rs727503453

chr15-43618088-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_153700.2(STRC):c.333G>T(p.Gly111=) 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.675

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 15-43618088-C-A is Benign according to our data. Variant chr15-43618088-C-A is described in ClinVar as [Benign]. Clinvar id is 165325.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-43618088-C-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.675 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRC	NM_153700.2	c.333G>T	p.Gly111=	synonymous_variant	2/29	ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7	c.333G>T	p.Gly111=	synonymous_variant	2/29	5	NM_153700.2	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1380 AN: 130064 Hom.: 0 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00283

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: 0.0000645

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00244 AC: 348 AN: 142582 Hom.: 0 AF XY: 0.00191 AC XY: 148 AN XY: 77544

Gnomad AFR exome AF: 0.0462

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000531

Gnomad OTH exome AF: 0.000943

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00116 AC: 1600 AN: 1379144 Hom.: 0 Cov.: 22 AF XY: 0.000942 AC XY: 647 AN XY: 687124

Gnomad4 AFR exome AF: 0.0454

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000367

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000104

Gnomad4 OTH exome AF: 0.00281

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0106 AC: 1379 AN: 130192 Hom.: 0 Cov.: 17 AF XY: 0.0100 AC XY: 630 AN XY: 62944

Gnomad4 AFR AF: 0.0412

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000645

Gnomad4 OTH AF: 0.00752

Alfa AF: 0.00710 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 26, 2013

Gly111Gly in Exon 02 of STRC: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 3.9% (16/408) of chrom osomes from African populations by the 1000Genomes project (as reported in the D eafness Variation Database: http://deafnessvariationdatabase.org). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	9.9
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs727503453; hg19: chr15-43910286;