Genetic Variant NM_153700.2:c.678A>G (chr15-43617743-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_153700.2(STRC):c.678A>G(p.Thr226Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T226T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 16)

Failed GnomAD Quality Control

Consequence

STRC
NM_153700.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=-1.31 with no splicing effect.

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.678A>G	p.Thr226Thr	synonymous	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.678A>G	p.Thr226Thr	synonymous	Exon 2 of 29	ENSP00000401513.2
STRC	ENST00000440125.5	TSL:1	n.678A>G		non_coding_transcript_exon	Exon 2 of 28	ENSP00000394866.1
ENSG00000284772	ENST00000643290.1		n.*841A>G		non_coding_transcript_exon	Exon 4 of 9	ENSP00000495476.1

Frequencies

GnomAD3 genomes

AF:

0.0000229

AC:

AN:

131150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000709

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

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000229

AC:

AN:

131258

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

63370

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

32036

American (AMR)

AF:

0.00

AC:

AN:

13474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3278

East Asian (EAS)

AF:

0.000711

AC:

AN:

4220

South Asian (SAS)

AF:

0.00

AC:

AN:

3342

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62496

Other (OTH)

AF:

0.00

AC:

AN:

1736

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000468493), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.308

Heterozygous variant carriers

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.9

(source)

DANN

Benign

0.51

PhyloP100

-1.3

PromoterAI

0.0046

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over