VCV003156043.2 - ClinVar

NM_001035006.5(RPL17):c.167A>T (p.Gln56Leu)

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.

(2)

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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001035006.5(RPL17):c.167A>T (p.Gln56Leu)

Variation ID: 3156043 Accession: VCV003156043.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 18q21.1 18: 49490842 (GRCh38) [ NCBI UCSC ] 18: 47017212 (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	May 1, 2024	Aug 18, 2024	Feb 27, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001035006.5:c.167A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001030178.1:p.Gln56Leu	missense
NM_000985.5:c.167A>T	NP_000976.1:p.Gln56Leu	missense
NM_001199340.2:c.167A>T	NP_001186269.1:p.Gln56Leu	missense
NM_001199341.3:c.167A>T	NP_001186270.1:p.Gln56Leu	missense
NM_001199342.3:c.167A>T	NP_001186271.1:p.Gln56Leu	missense
NM_001199343.3:c.167A>T	NP_001186272.1:p.Gln56Leu	missense
NM_001199344.3:c.167A>T	NP_001186273.1:p.Gln56Leu	missense
NM_001199345.2:c.53A>T	NP_001186274.1:p.Gln18Leu	missense
NM_001199355.1:c.167A>T	NP_001186284.1:p.Gln56Leu	missense
NM_001199356.2:c.53A>T	NP_001186285.1:p.Gln18Leu	missense
NM_001369555.1:c.182A>T	NP_001356484.1:p.Gln61Leu	missense
NM_001369556.1:c.167A>T	NP_001356485.1:p.Gln56Leu	missense
NM_001369557.1:c.167A>T	NP_001356486.1:p.Gln56Leu	missense
NM_001369558.1:c.167A>T	NP_001356487.1:p.Gln56Leu	missense
NM_001369560.1:c.137A>T	NP_001356489.1:p.Gln46Leu	missense
NM_001369561.1:c.137A>T	NP_001356490.1:p.Gln46Leu	missense
NM_001369562.1:c.53A>T	NP_001356491.1:p.Gln18Leu	missense
NM_001369563.1:c.53A>T	NP_001356492.1:p.Gln18Leu	missense
NC_000018.10:g.49490842T>A
NC_000018.9:g.47017212T>A

... more HGVS ... less HGVS

Protein change

Q18L, Q56L, Q61L, Q46L

Other names

Canonical SPDI

NC_000018.10:49490841:T: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

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.
RPL17		-	-	GRCh38 GRCh37	-	45
RPL17-C18orf32	-	-	-	GRCh38 GRCh37	-	48

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 specified	Uncertain significance (1)	criteria provided, single submitter	Feb 27, 2024	RCV004451921.1
Diamond-Blackfan anemia	Likely benign (1)	no assertion criteria provided	Apr 26, 2024	RCV004691642.1

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 (Feb 27, 2024)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV005015431.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: The c.167A>T (p.Q56L) alteration is located in exon 4 (coding exon 3) of the RPL17 gene. This alteration results from a A to T substitution … (more) The c.167A>T (p.Q56L) alteration is located in exon 4 (coding exon 3) of the RPL17 gene. This alteration results from a A to T substitution at nucleotide position 167, causing the glutamine (Q) at amino acid position 56 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
Likely benign (Apr 26, 2024)	no assertion criteria provided Method: research	Diamond-Blackfan anemia Affected status: yes, not applicable Allele origin: unknown, not applicable	Advanced Center For Translational And Genetic Medicine, Ann & Robert H. Lurie Children's Hospital Of Chicago Accession: SCV005038800.1 First in ClinVar: Aug 18, 2024 Last updated: Aug 18, 2024	Publications: PubMed (1) PubMed: 39088281 Observation 1: Observation 2: Method: in vivo complementation assay in zebrafish Result: variant rescues rpl17 morpholino similar to wild type

Comment:

The c.167A>T (p.Q56L) alteration is located in exon 4 (coding exon 3) of the RPL17 gene. This alteration results from a A to T substitution at nucleotide position 167, causing the glutamine (Q) at amino acid position 56 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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
An atypical form of 60S ribosomal subunit in Diamond-Blackfan anemia linked to RPL17 variants.	Fellmann F	JCI insight	2024	PMID: 39088281

Text-mined citations for this variant ...

Record last updated Sep 17, 2024

ClinVar Genomic variation as it relates to human health

NM_001035006.5(RPL17):c.167A>T (p.Gln56Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...