VCV002443812.1 - ClinVar

NM_032236.8(USP48):c.1216G>A (p.Gly406Arg)

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_032236.8(USP48):c.1216G>A (p.Gly406Arg)

Variation ID: 2443812 Accession: VCV002443812.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p36.12 1: 21729788 (GRCh38) [ NCBI UCSC ] 1: 22056281 (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	Mar 18, 2023	Mar 18, 2023	Jan 27, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_032236.8:c.1216G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_115612.4:p.Gly406Arg	missense
NM_001032730.3:c.1216G>A	NP_001027902.1:p.Gly406Arg	missense
NM_001330394.3:c.1216G>A	NP_001317323.1:p.Gly406Arg	missense
NM_001350164.2:c.1213G>A	NP_001337093.1:p.Gly405Arg	missense
NM_001350166.2:c.1213G>A	NP_001337095.1:p.Gly405Arg	missense
NM_001350167.2:c.1213G>A	NP_001337096.1:p.Gly405Arg	missense
NM_001350168.2:c.1216G>A	NP_001337097.1:p.Gly406Arg	missense
NC_000001.11:g.21729788C>T
NC_000001.10:g.22056281C>T
NG_047203.1:g.58412G>A

... more HGVS ... less HGVS

Protein change

G405R

Other names

G406R

Canonical SPDI

NC_000001.11:21729787:C:T

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

OMIM: 617445.0001 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.
USP48		-	-	GRCh38 GRCh37	45	60

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.
Hearing loss, autosomal dominant 85	Pathogenic (1)	no assertion criteria provided	Jan 27, 2023	RCV003152419.1

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 (Jan 27, 2023)	no assertion criteria provided Method: literature only	DEAFNESS, AUTOSOMAL DOMINANT 85 Affected status: not provided Allele origin: germline	OMIM Accession: SCV003841010.1 First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023	Publications: PubMed (1) PubMed: 34059922 Comment on evidence: In 5 affected members over 3 generations of an Italian family with autosomal dominant nonsyndromic sensorineural hearing loss (DFNA85; 620227), Bassani et al. (2021) identified … (more) In 5 affected members over 3 generations of an Italian family with autosomal dominant nonsyndromic sensorineural hearing loss (DFNA85; 620227), Bassani et al. (2021) identified heterozygosity for a c.1216G-A transition (c.1216G-A, NM_032234.7) in the USP48 gene, resulting in a gly406-to-arg (G406R) substitution within a flexible loop that flanks the catalytic site of the hydrolase. The mutation was not found in 2 unaffected family members, but was present in 1 unaffected individual, indicating incomplete penetrance. The variant was also present in gnomAD, at low minor allele frequency (MAF 6.7 x 10(-5)) and only in heterozygosity. Analysis using HEK293T cells expressing the G406R mutant showed an impaired ability to cleave tetraubiquitin into tri-, di-, and monoubiquitin with the mutant compared to wildtype USP48. (less)

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
Variants in USP48 encoding ubiquitin hydrolase are associated with autosomal dominant non-syndromic hereditary hearing loss.	Bassani S	Human molecular genetics	2021	PMID: 34059922

Text-mined citations for this variant ...

Record last updated Sep 01, 2024

ClinVar Genomic variation as it relates to human health

NM_032236.8(USP48):c.1216G>A (p.Gly406Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...