rs139848805

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_153700.2(STRC):c.498G>A(p.Pro166Pro) 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.343

Publications

1 publications found

Variant links:

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]

STRC Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 16
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

STRC links:

ENSG00000284772 (HGNC:):

ENSG00000284772 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 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 Benign/Likely_benign. ClinVar VariationId is 165324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.343 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.498G>A	p.Pro166Pro	synonymous_variant	Exon 2 of 29	ENST00000450892.7	NP_714544.1	Q7RTU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STRC	ENST00000450892.7 link	c.498G>A	p.Pro166Pro	synonymous_variant	Exon 2 of 29	5	NM_153700.2	ENSP00000401513.2	Q7RTU9
ENSG00000284772	ENST00000643290.1 link	n.*661G>A		non_coding_transcript_exon_variant	Exon 4 of 9			ENSP00000495476.1	A0A2R8Y6Q2
ENSG00000284772	ENST00000643290.1 link	n.*661G>A		3_prime_UTR_variant	Exon 4 of 9			ENSP00000495476.1	A0A2R8Y6Q2

Frequencies

GnomAD3 genomes

AF:

0.00468

AC:

711

AN:

151912

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00566

AC:

1417

AN:

250414

AF XY:

0.00593

show subpopulations

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 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.:

Cov.:

AF XY:

0.00655

AC XY:

4745

AN XY:

724350

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00161

AC:

AN:

33460

American (AMR)

AF:

0.00179

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00513

AC:

134

AN:

26110

East Asian (EAS)

AF:

0.000353

AC:

AN:

39698

South Asian (SAS)

AF:

0.000916

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00817

AC:

436

AN:

53344

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00765

AC:

8467

AN:

1106196

Other (OTH)

AF:

0.00546

AC:

329

AN:

60202

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.251

Heterozygous variant carriers

1247

2494

3740

4987

6234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00468

AC:

711

AN:

152030

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74344

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00209

AC:

AN:

41552

American (AMR)

AF:

0.00321

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00404

AC:

AN:

3466

East Asian (EAS)

AF:

0.00193

AC:

AN:

5194

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00472

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00724

AC:

491

AN:

67786

Other (OTH)

AF:

0.00331

AC:

AN:

2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.280

Heterozygous variant carriers

119

178

238

297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00624

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

May 19, 2017

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

STRC: BP4, BP7 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive nonsyndromic hearing loss 16

Benign:1

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

-0.34

PromoterAI

0.019

Neutral

(source)

Mutation Taster

=299/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over