Genetic Variant STRC:p.Phe60Tyr (chr15-43618242-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153700.2(STRC):c.179T>A(p.Phe60Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F60S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 11)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.27

Publications

11 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14026219).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153700.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	NM_153700.2	MANE Select	c.179T>A	p.Phe60Tyr	missense	Exon 2 of 29	NP_714544.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STRC	ENST00000450892.7	TSL:5 MANE Select	c.179T>A	p.Phe60Tyr	missense	Exon 2 of 29	ENSP00000401513.2
STRC	ENST00000440125.5	TSL:1	n.179T>A		non_coding_transcript_exon	Exon 2 of 28	ENSP00000394866.1
ENSG00000284772	ENST00000643290.1		n.*342T>A		non_coding_transcript_exon	Exon 4 of 9	ENSP00000495476.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

556900

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

293870

African (AFR)

AF:

0.00

AC:

AN:

14698

American (AMR)

AF:

0.00

AC:

AN:

28932

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16768

East Asian (EAS)

AF:

0.00

AC:

AN:

31844

South Asian (SAS)

AF:

0.00

AC:

AN:

53662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

348046

Other (OTH)

AF:

0.00

AC:

AN:

29958

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.030

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.33

M_CAP

Benign

0.041

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.87

PhyloP100

3.3

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.090

REVEL

Benign

0.23

Sift

Uncertain

0.028

Sift4G

Benign

0.41

Polyphen

0.0010

Vest4

0.26

MutPred

0.16

Gain of phosphorylation at F60 (P = 0.0982)

MVP

0.42

ClinPred

0.13

GERP RS

3.4

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.075

gMVP

0.38

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over