VCV000235130.3 - ClinVar

NM_006016.6(CD164):c.574C>T (p.Arg192Ter)

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.

no classifications from unflagged records

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_006016.6(CD164):c.574C>T (p.Arg192Ter)

Variation ID: 235130 Accession: VCV000235130.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6q21 6: 109368871 (GRCh38) [ NCBI UCSC ] 6: 109690074 (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 4, 2016	Oct 7, 2023	Apr 25, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_006016.6:c.574C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_006007.2:p.Arg192Ter	nonsense
NM_001142401.3:c.535C>T	NP_001135873.1:p.Arg179Ter	nonsense
NM_001142402.3:c.517C>T	NP_001135874.1:p.Arg173Ter	nonsense
NM_001142403.3:c.523+51C>T		intron variant
NM_001142404.3:c.428-546C>T		intron variant
NM_001346500.2:c.472C>T	NP_001333429.1:p.Arg158Ter	nonsense
NC_000006.12:g.109368871G>A
NC_000006.11:g.109690074G>A
NG_051926.1:g.18942C>T
LRG_1419:g.18942C>T
LRG_1419t1:c.574C>T	LRG_1419p1:p.Arg192Ter

... more HGVS ... less HGVS

Protein change

R192*, R173*, R158*, R179*

Other names

Canonical SPDI

NC_000006.12:109368870: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: CA10581228 OMIM: 603356.0001 dbSNP: rs876661402 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.
CD164		-	-	GRCh38 GRCh37	91	124

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.
Autosomal dominant nonsyndromic hearing loss 66	no classifications from unflagged records (2)	no classifications from unflagged records	Apr 25, 2024	RCV000223938.5

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 (Jul 30, 2019)	Flagged submission flagged submission Method: literature only Reason: Other Notes: Flagging candidate with (...more) Source: ClinGen	DEAFNESS, AUTOSOMAL DOMINANT 66 (1 family) Affected status: not provided Allele origin: germline	OMIM Accession: SCV000280566.2 First in ClinVar: Jun 04, 2016 Last updated: Aug 04, 2019	Publications: PubMed (1) PubMed: 26197441 Comment on evidence: In affected members of a multigenerational Dutch family with autosomal dominant deafness-66 (DFNA66; 616969), Nyegaard et al. (2015) identified a heterozygous c.574C-T transition (c.574C-T, NM_006016.4) … (more) In affected members of a multigenerational Dutch family with autosomal dominant deafness-66 (DFNA66; 616969), Nyegaard et al. (2015) identified a heterozygous c.574C-T transition (c.574C-T, NM_006016.4) at the end of exon 6 of the CD164 gene, resulting in an arg192-to-ter (R192X) substitution and the deletion of highly conserved residues in the C terminus that include the sorting motif. The mutation was predicted to affect only the membrane-bound isoforms (isoforms 1-3). The mutation, which was found by a combination of linkage analysis and candidate gene sequencing, segregated with the disorder in the family and was not found in any public database or in 1,200 unrelated Dutch control individuals. Transfection of the mutation into HEK293 cells showed that the mutant protein was located mostly at the plasma membrane, whereas the wildtype protein was predominantly located in intracellular vesicles, indicating abnormal intracellular trafficking of the mutant protein. Immunoprecipitation studies showed that the mutant protein was expressed and that it colocalized and formed heterodimers with wildtype CD164. However, there was no evidence of a dominant-negative effect on wildtype internalization. (less)
Likely pathogenic (Jan 07, 2023)	Flagged submission flagged submission (ACMG Guidelines, 2015) Method: clinical testing Reason: Other Notes: Flagging candidate with (...more) Source: ClinGen	Autosomal dominant nonsyndromic hearing loss 66 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004041016.1 First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023
Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A Novel Locus Harbouring a Functional CD164 Nonsense Mutation Identified in a Large Danish Family with Nonsyndromic Hearing Impairment.	Nyegaard M	PLoS genetics	2015	PMID: 26197441

Text-mined citations for rs876661402 ...

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 Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_006016.6(CD164):c.574C>T (p.Arg192Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs876661402 ...