VCV002506044.1 - ClinVar

NM_021615.5(CHST6):c.573dup (p.Ala192fs)

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.

(1)

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.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_021615.5(CHST6):c.573dup (p.Ala192fs)

Variation ID: 2506044 Accession: VCV002506044.1

Type and length

Duplication, 1 bp

Location

Cytogenetic: 16q23.1 16: 75479255-75479256 (GRCh38) [ NCBI UCSC ] 16: 75513153-75513154 (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	Jun 24, 2023	Jun 24, 2023	May 18, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_021615.5:c.573dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_067628.1:p.Ala192fs	frameshift
NC_000016.10:g.75479259dup
NC_000016.9:g.75513157dup
NG_016442.2:g.21186dup
LRG_1252:g.21186dup
LRG_1252t1:c.573dup	LRG_1252p1:p.Ala192fs

... more HGVS ... less HGVS

Protein change

A192fs

Other names

Canonical SPDI

NC_000016.10:75479255:GGGG:GGGGG

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.
CHST6		-	-	GRCh38 GRCh37	298	349

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.
Macular corneal dystrophy	Pathogenic (1)	criteria provided, single submitter	May 18, 2023	RCV003236275.1

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.
Pathogenic (May 18, 2023)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Macular corneal dystrophy Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV003933991.1 First in ClinVar: Jun 24, 2023 Last updated: Jun 24, 2023	Publications: PubMed (2) PubMed: 16568029‚ 30716718 Comment: Variant summary: CHST6 c.573dupC (p.Ala192ArgfsX30) results in a premature termination codon in the last exon of the gene and although nonsense mediated decay is not … (more) Variant summary: CHST6 c.573dupC (p.Ala192ArgfsX30) results in a premature termination codon in the last exon of the gene and although nonsense mediated decay is not expected, it is predicted to cause a truncation of the encoded protein, a commonly known mechanism for disease. Variants downstream of this position have been classified as pathogenic. The variant allele was found at a frequency of 4e-06 in 247332 control chromosomes (gnomAD). c.573dupC has been reported in the literature in at least one individual affected with Macular Corneal Dystrophy (e.g. Klintworth_2006). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16568029, 30716718). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. (less)

Comment:

Variant summary: CHST6 c.573dupC (p.Ala192ArgfsX30) results in a premature termination codon in the last exon of the gene and although nonsense mediated decay is not expected, it is predicted to cause a truncation of the encoded protein, a commonly known mechanism for disease. Variants downstream of this position have been classified as pathogenic. The variant allele was found at a frequency of 4e-06 in 247332 control chromosomes (gnomAD). c.573dupC has been reported in the literature in at least one individual affected with Macular Corneal Dystrophy (e.g. Klintworth_2006). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16568029, 30716718). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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
A comprehensive evaluation of 181 reported CHST6 variants in patients with macular corneal dystrophy.	Zhang J	Aging	2019	PMID: 30716718
CHST6 mutations in North American subjects with macular corneal dystrophy: a comprehensive molecular genetic review.	Klintworth GK	Molecular vision	2006	PMID: 16568029

Text-mined citations for this variant ...

Record last updated Jun 24, 2023

ClinVar Genomic variation as it relates to human health

NM_021615.5(CHST6):c.573dup (p.Ala192fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...