VCV000194930.11 - ClinVar

NM_001330078.2(NRXN1):c.3499C>T (p.Arg1167Ter)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(4)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Pathogenic(1); Likely pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001330078.2(NRXN1):c.3499C>T (p.Arg1167Ter)

Variation ID: 194930 Accession: VCV000194930.11

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2p16.3 2: 50236836 (GRCh38) [ NCBI UCSC ] 2: 50463974 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 19, 2017	Sep 29, 2024	May 30, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001330078.2:c.3499C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001317007.1:p.Arg1167Ter	nonsense
NM_001135659.3:c.3619C>T	NP_001129131.1:p.Arg1207Ter	nonsense
NM_001330077.2:c.3475C>T	NP_001317006.1:p.Arg1159Ter	nonsense
NM_001330082.2:c.3475C>T	NP_001317011.1:p.Arg1159Ter	nonsense
NM_001330083.2:c.3433C>T	NP_001317012.1:p.Arg1145Ter	nonsense
NM_001330084.2:c.3433C>T	NP_001317013.1:p.Arg1145Ter	nonsense
NM_001330085.2:c.3472C>T	NP_001317014.1:p.Arg1158Ter	nonsense
NM_001330086.2:c.3499C>T	NP_001317015.1:p.Arg1167Ter	nonsense
NM_001330087.2:c.3388C>T	NP_001317016.1:p.Arg1130Ter	nonsense
NM_001330088.2:c.3418C>T	NP_001317017.1:p.Arg1140Ter	nonsense
NM_001330091.2:c.394C>T	NP_001317020.1:p.Arg132Ter	nonsense
NM_001330092.2:c.394C>T	NP_001317021.1:p.Arg132Ter	nonsense
NM_001330093.2:c.3496C>T	NP_001317022.1:p.Arg1166Ter	nonsense
NM_001330094.2:c.3487C>T	NP_001317023.1:p.Arg1163Ter	nonsense
NM_001330095.2:c.3448C>T	NP_001317024.1:p.Arg1150Ter	nonsense
NM_001330096.2:c.3388C>T	NP_001317025.1:p.Arg1130Ter	nonsense
NM_001330097.2:c.394C>T	NP_001317026.1:p.Arg132Ter	nonsense
NM_004801.6:c.3499C>T	NP_004792.1:p.Arg1167Ter	nonsense
NM_138735.5:c.394C>T	NP_620072.1:p.Arg132Ter	nonsense
NC_000002.12:g.50236836G>A
NC_000002.11:g.50463974G>A
NG_011878.1:g.800701C>T

... more HGVS ... less HGVS

Protein change

R1207*, R1140*, R1150*, R132*, R1158*, R1163*, R1166*, R1167*, R1159*, R1130*, R1145*

Other names

Canonical SPDI

NC_000002.12:50236835:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA241167 dbSNP: rs199546979 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
NRXN1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2325	2391

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	May 30, 2024	RCV000522614.8
Obesity	Likely pathogenic (1)	no assertion criteria provided	Jul 1, 2018	RCV000787967.3
Pitt-Hopkins-like syndrome 2	Pathogenic (1)	criteria provided, single submitter	Jan 25, 2021	RCV002466460.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Jun 12, 2018)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000226888.5 First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=NRXN1 Number of individuals with the variant: 1 Sex: mixed
Pathogenic (Jan 25, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pitt-Hopkins-like syndrome 2 Affected status: yes Allele origin: germline	Genetics and Molecular Pathology, SA Pathology Additional submitter: Shariant Australia, Australian Genomics Accession: SCV002761514.1 First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022
Likely pathogenic (May 30, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000618356.3 First in ClinVar: Dec 19, 2017 Last updated: Sep 29, 2024	Comment: Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more) Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Identified in the heterozygous state in an individual with autism, epilepsy, and developmental delay, although the inheritance is unknown (PMID: 29056246); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29056246) (less)
Likely pathogenic (Jul 01, 2018)	no assertion criteria provided Method: research	Obesity Affected status: yes Allele origin: germline	Dash Lab, University Health Network Accession: SCV000914238.1 First in ClinVar: Jul 22, 2019 Last updated: Jul 22, 2019 Comment: Single case. Extreme obesity, non-specific learning disorder, anxiety and depression	Age: 20-30 years Sex: female

Comment:

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Identified in the heterozygous state in an individual with autism, epilepsy, and developmental delay, although the inheritance is unknown (PMID: 29056246); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29056246)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=NRXN1	-	-	-	-

Text-mined citations for rs199546979 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_001330078.2(NRXN1):c.3499C>T (p.Arg1167Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs199546979 ...