rs139848805

Variant names:

• chr15-43617923-C-T
• rs139848805
• NM_153700.2:c.498G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_153700.2(STRC):​c.498G>A​(p.Pro166Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0066 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.343
• Publications: 1 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

ENSG00000284772 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 15-43617923-C-T is Benign according to our data. Variant chr15-43617923-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 165324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.343 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	NM_153700.2	MANE Select	c.498G>A	p.Pro166Pro	synonymous	Exon 2 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.498G>A	p.Pro166Pro	synonymous	Exon 2 of 29	ENSP00000401513.2	Q7RTU9
	STRC	ENST00000440125.5	TSL:1	n.498G>A		non_coding_transcript_exon	Exon 2 of 28	ENSP00000394866.1	E7EPM8
	ENSG00000284772	ENST00000643290.1		n.*661G>A		non_coding_transcript_exon	Exon 4 of 9	ENSP00000495476.1	A0A2R8Y6Q2

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 711 AN: 151912 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00210

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00724

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00566 AC: 1417 AN: 250414 AF XY: 0.00593

Gnomad AFR exome AF: 0.00206

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00537

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.00685

Gnomad NFE exome AF: 0.00924

Gnomad OTH exome AF: 0.00654

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00659 AC: 9594 AN: 1455708 Hom.: 0 Cov.: 31 AF XY: 0.00655 AC XY: 4745 AN XY: 724350

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

African (AFR) AF: 0.00161 AC: 54 AN: 33460

American (AMR) AF: 0.00179 AC: 80 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00513 AC: 134 AN: 26110

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39698

South Asian (SAS) AF: 0.000916 AC: 79 AN: 86230

European-Finnish (FIN) AF: 0.00817 AC: 436 AN: 53344

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00765 AC: 8467 AN: 1106196

Other (OTH) AF: 0.00546 AC: 329 AN: 60202

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00468 AC: 711 AN: 152030 Hom.: 0 Cov.: 19 AF XY: 0.00430 AC XY: 320 AN XY: 74344

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

African (AFR) AF: 0.00209 AC: 87 AN: 41552

American (AMR) AF: 0.00321 AC: 49 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00472 AC: 50 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00724 AC: 491 AN: 67786

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00624 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		-0.34
PromoterAI		0.019	Neutral
Mutation Taster		=299/1	polymorphism

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: rs139848805; hg19: chr15-43910121;