rs1308469405

chr15-43614438-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_153700.2(STRC):c.2172T>C(p.Val724=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 7)
  • Exomes 𝑓: 0.0000052 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.665

Genes affected

STRC (HGNC:16035): (stereocilin) This gene encodes a protein that is associated with the hair bundle of the sensory hair cells in the inner ear. The hair bundle is composed of stiff microvilli called stereocilia and is involved with mechanoreception of sound waves. This gene is part of a tandem duplication on chromosome 15; the second copy is a pseudogene. Mutations in this gene cause autosomal recessive non-syndromic deafness. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 15-43614438-A-G is Benign according to our data. Variant chr15-43614438-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 505236.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.665 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRC	NM_153700.2	c.2172T>C	p.Val724=	synonymous_variant	5/29	ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7	c.2172T>C	p.Val724=	synonymous_variant	5/29	5	NM_153700.2	P2
STRC	ENST00000440125.5	c.*174T>C		3_prime_UTR_variant, NMD_transcript_variant	6/28	1
STRC	ENST00000541030.5	c.63T>C	p.Val21=	synonymous_variant	5/27	5		A2
STRC	ENST00000428650.5	c.2172T>C	p.Val724=	synonymous_variant, NMD_transcript_variant	5/28	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 64520 Hom.: 0 Cov.: 7 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000517 AC: 3 AN: 580700 Hom.: 0 Cov.: 7 AF XY: 0.00000651 AC XY: 2 AN XY: 307056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000754

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000262

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000155 AC: 1 AN: 64520 Hom.: 0 Cov.: 7 AF XY: 0.0000326 AC XY: 1 AN XY: 30640

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000253 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 02, 2016

p.Val724Val in exon 5 of STRC: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and it is not located within the splice consensus sequence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	8.7
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1308469405; hg19: chr15-43906636;