rs727503451

Variant names:

• chr15-43616686-C-T
• rs727503451
• NM_153700.2:c.880G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_153700.2(STRC):​c.880G>A​(p.Val294Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., cov: 13)
  • Exomes 𝑓: 0.000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.969

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037196666).
• BP6: Variant 15-43616686-C-T is Benign according to our data. Variant chr15-43616686-C-T is described in ClinVar as [Benign]. Clinvar id is 165322.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2	c.880G>A	p.Val294Ile	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.880G>A	p.Val294Ile	missense_variant	Exon 4 of 29	5	NM_153700.2	ENSP00000401513.2
ENSG00000284772	ENST00000643290.1	n.*1043G>A		non_coding_transcript_exon_variant	Exon 6 of 9			ENSP00000495476.1
ENSG00000284772	ENST00000643290.1	n.*1043G>A		3_prime_UTR_variant	Exon 6 of 9			ENSP00000495476.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4 AN: 109592 Hom.: 0 Cov.: 13 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000931

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: 0.0000550

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000275 AC: 11 AN: 399846 Hom.: 0 Cov.: 0 AF XY: 0.0000332 AC XY: 7 AN XY: 210720

Gnomad4 AFR exome AF: 0.0000931

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000365

Gnomad4 SAS exome AF: 0.0000673

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000365 AC: 4 AN: 109592 Hom.: 0 Cov.: 13 AF XY: 0.0000195 AC XY: 1 AN XY: 51326

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000931

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000550

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 05, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Val294Ile in Exon 04 of STRC: This variant is not expected to have clinical sign ificance due to a lack of conservation across species, including mammals. Of not e, several mammals have an isoleucine at this position despite high nearby amino acid conservation. In addition, computational analyses (PolyPhen2, SIFT, AlignG VGD) do not suggest a high likelihood of impact to the protein. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.084
DANN	Benign	0.71
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.070
MutPred		0.21		Gain of helix (P = 0.132);.;
MVP		0.33
ClinPred		0.030	T
GERP RS		-9.9
Varity_R		0.022
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs727503451; hg19: chr15-43908884;