15-43618042-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153700.2(STRC):c.379C>G(p.Arg127Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 19)
• Consequence: STRC NM_153700.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27646917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRC	NM_153700.2	c.379C>G	p.Arg127Gly	missense_variant	2/29	ENST00000450892.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRC	ENST00000450892.7	c.379C>G	p.Arg127Gly	missense_variant	2/29	5	NM_153700.2	P2

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.066	T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.011
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.73	T
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	N;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.017	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.49	P;.
Vest4		0.35
MutPred		0.26		Gain of sheet (P = 0.0149);.;
MVP		0.80
ClinPred		0.47	T
GERP RS		2.7
Varity_R		0.14
gMVP		0.62

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: rs771264491; hg19: chr15-43910240;