rs150548868

Variant names:

• chr15-43607955-C-T
• rs62018890
• NM_153700.2:c.3702G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_153700.2(STRC):​c.3702G>A​(p.Glu1234Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,608,708 control chromosomes in the GnomAD database, including 28,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2535 hom., cov: 22)
  • Exomes 𝑓: 0.17 (25578 hom.)
• Consequence: STRC NM_153700.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.659
• Publications: 6 publications found

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: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 15-43607955-C-T is Benign according to our data. Variant chr15-43607955-C-T is described in ClinVar as Benign. ClinVar VariationId is 165313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.659 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	NM_153700.2	MANE Select	c.3702G>A	p.Glu1234Glu	synonymous	Exon 18 of 29	NP_714544.1	Q7RTU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	ENST00000450892.7	TSL:5 MANE Select	c.3702G>A	p.Glu1234Glu	synonymous	Exon 18 of 29	ENSP00000401513.2	Q7RTU9
	STRC	ENST00000440125.5	TSL:1	n.*1494G>A		non_coding_transcript_exon	Exon 17 of 28	ENSP00000394866.1	E7EPM8
	STRC	ENST00000440125.5	TSL:1	n.*1494G>A		3_prime_UTR	Exon 17 of 28	ENSP00000394866.1	E7EPM8

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23036 AN: 148428 Hom.: 2525 Cov.: 22

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.165

GnomAD2 exomes AF: 0.147 AC: 36858 AN: 250804 AF XY: 0.152

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.0972

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.00245

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.168 AC: 245812 AN: 1460164 Hom.: 25578 Cov.: 33 AF XY: 0.169 AC XY: 123111 AN XY: 726476

African (AFR) AF: 0.156 AC: 5136 AN: 32910

American (AMR) AF: 0.101 AC: 4525 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5193 AN: 26094

East Asian (EAS) AF: 0.00134 AC: 53 AN: 39634

South Asian (SAS) AF: 0.181 AC: 15639 AN: 86210

European-Finnish (FIN) AF: 0.110 AC: 5848 AN: 53388

Middle Eastern (MID) AF: 0.248 AC: 1428 AN: 5752

European-Non Finnish (NFE) AF: 0.178 AC: 197923 AN: 1111170

Other (OTH) AF: 0.167 AC: 10067 AN: 60308

GnomAD4 genome AF: 0.155 AC: 23070 AN: 148544 Hom.: 2535 Cov.: 22 AF XY: 0.152 AC XY: 11006 AN XY: 72580

African (AFR) AF: 0.156 AC: 6048 AN: 38816

American (AMR) AF: 0.140 AC: 2108 AN: 15040

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 669 AN: 3438

East Asian (EAS) AF: 0.00137 AC: 7 AN: 5116

South Asian (SAS) AF: 0.153 AC: 728 AN: 4758

European-Finnish (FIN) AF: 0.103 AC: 1079 AN: 10426

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.176 AC: 11913 AN: 67676

Other (OTH) AF: 0.163 AC: 337 AN: 2070

Alfa AF: 0.172 Hom.: 511

Bravo AF: 0.156

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 16 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.2
DANN	Benign	0.79
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62018890; hg19: chr15-43900153; COSMIC: COSV68659796; COSMIC: COSV68659796;