rs139848805

Positions:

• chr15-43617923-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_153700.2(STRC):​c.498G>A​(p.Pro166=) 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 0.0047 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0066 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.343

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 15-43617923-C-T is Benign according to our data. Variant chr15-43617923-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 165324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-43617923-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.343 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00468 (711/152030) while in subpopulation NFE AF= 0.00724 (491/67786). AF 95% confidence interval is 0.00671. There are 0 homozygotes in gnomad4. There are 320 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRC	NM_153700.2	c.498G>A	p.Pro166=	synonymous_variant	2/29	ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7	c.498G>A	p.Pro166=	synonymous_variant	2/29	5	NM_153700.2	P2

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 711 AN: 151912 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00724

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00566 AC: 1417 AN: 250414 Hom.: 0 AF XY: 0.00593 AC XY: 803 AN XY: 135474

Gnomad AFR exome AF: 0.00206

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00537

Gnomad EAS exome AF: 0.000707

Gnomad SAS exome AF: 0.000817

Gnomad FIN exome AF: 0.00685

Gnomad NFE exome AF: 0.00924

Gnomad OTH exome AF: 0.00654

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00659 AC: 9594 AN: 1455708 Hom.: 0 Cov.: 31 AF XY: 0.00655 AC XY: 4745 AN XY: 724350

Gnomad4 AFR exome AF: 0.00161

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00513

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.000916

Gnomad4 FIN exome AF: 0.00817

Gnomad4 NFE exome AF: 0.00765

Gnomad4 OTH exome AF: 0.00546

GnomAD4 genome AF: 0.00468 AC: 711 AN: 152030 Hom.: 0 Cov.: 19 AF XY: 0.00430 AC XY: 320 AN XY: 74344

Gnomad4 AFR AF: 0.00209

Gnomad4 AMR AF: 0.00321

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00472

Gnomad4 NFE AF: 0.00724

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00624 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Pro166Pro 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 0.6% (40/7014) of Euro pean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs139848805). -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autosomal recessive nonsyndromic hearing loss 16 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs139848805; hg19: chr15-43910121;