15-43616655-G-C

Variant names:

• chr15-43616655-G-C
• rs727503448
• NM_153700.2:c.911C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153700.2(STRC):​c.911C>G​(p.Ala304Gly) variant causes a missense 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.

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 10)
  • Exomes 𝑓: 0.00035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27

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]

ENSG00000284772 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0085558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2	c.911C>G	p.Ala304Gly	missense_variant	Exon 4 of 29	ENST00000450892.7	NP_714544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7	c.911C>G	p.Ala304Gly	missense_variant	Exon 4 of 29	5	NM_153700.2	ENSP00000401513.2
ENSG00000284772	ENST00000643290.1	n.*1074C>G		non_coding_transcript_exon_variant	Exon 6 of 9			ENSP00000495476.1
ENSG00000284772	ENST00000643290.1	n.*1074C>G		3_prime_UTR_variant	Exon 6 of 9			ENSP00000495476.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 169 AN: 86450 Hom.: 0 Cov.: 10 FAILED QC

Gnomad AFR AF: 0.00841

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000971

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: 0.0000229

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000898 AC: 48 AN: 53470 Hom.: 0 AF XY: 0.000890 AC XY: 24 AN XY: 26980

Gnomad AFR exome AF: 0.00832

Gnomad AMR exome AF: 0.000386

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000166

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000354 AC: 152 AN: 429866 Hom.: 0 Cov.: 0 AF XY: 0.000327 AC XY: 74 AN XY: 226572

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.000607

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000224

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000233

Gnomad4 OTH exome AF: 0.000563

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00196 AC: 170 AN: 86532 Hom.: 0 Cov.: 10 AF XY: 0.00206 AC XY: 81 AN XY: 39390

Gnomad4 AFR AF: 0.00841

Gnomad4 AMR AF: 0.000969

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000229

Gnomad4 OTH AF: 0.00189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0086	T;T
MetaSVM	Benign	-0.43	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.47	N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.014	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.80	P;.
Vest4		0.46
MutPred		0.19		Loss of helix (P = 0.0167);.;
MVP		0.75
ClinPred		0.036	T
GERP RS		4.0
Varity_R		0.11
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs727503448; hg19: chr15-43908853;