rs727503453

Variant names:

• chr15-43618088-C-A
• rs727503453
• NM_153700.2:c.333G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_153700.2(STRC):​c.333G>T​(p.Gly111Gly) 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.675
• Publications: 0 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: Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000284772 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 15-43618088-C-A is Benign according to our data. Variant chr15-43618088-C-A is described in ClinVar as Benign. ClinVar VariationId is 165325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.675 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.333G>T	p.Gly111Gly	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.333G>T	p.Gly111Gly	synonymous	Exon 2 of 29	ENSP00000401513.2	Q7RTU9
	STRC	ENST00000440125.5	TSL:1	n.333G>T		non_coding_transcript_exon	Exon 2 of 28	ENSP00000394866.1	E7EPM8
	ENSG00000284772	ENST00000643290.1		n.*496G>T		non_coding_transcript_exon	Exon 4 of 9	ENSP00000495476.1	A0A2R8Y6Q2

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1380 AN: 130064 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00283

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: 0.0000645

Gnomad OTH AF: 0.00764

GnomAD2 exomes AF: 0.00244 AC: 348 AN: 142582 AF XY: 0.00191

Gnomad AFR exome AF: 0.0462

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000531

Gnomad OTH exome AF: 0.000943

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00116 AC: 1600 AN: 1379144 Hom.: 0 Cov.: 22 AF XY: 0.000942 AC XY: 647 AN XY: 687124

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

African (AFR) AF: 0.0454 AC: 1351 AN: 29732

American (AMR) AF: 0.00179 AC: 72 AN: 40286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25208

East Asian (EAS) AF: 0.00 AC: 0 AN: 38060

South Asian (SAS) AF: 0.0000367 AC: 3 AN: 81746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48778

Middle Eastern (MID) AF: 0.000402 AC: 2 AN: 4974

European-Non Finnish (NFE) AF: 0.0000104 AC: 11 AN: 1053008

Other (OTH) AF: 0.00281 AC: 161 AN: 57352

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0106 AC: 1379 AN: 130192 Hom.: 0 Cov.: 17 AF XY: 0.0100 AC XY: 630 AN XY: 62944

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

African (AFR) AF: 0.0412 AC: 1326 AN: 32206

American (AMR) AF: 0.00275 AC: 36 AN: 13092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3244

East Asian (EAS) AF: 0.00 AC: 0 AN: 3986

South Asian (SAS) AF: 0.00 AC: 0 AN: 3664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.0000645 AC: 4 AN: 61990

Other (OTH) AF: 0.00752 AC: 13 AN: 1728

⚠️ 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: 0.00710 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	9.9
DANN	Benign	0.85
PhyloP100		0.68
PromoterAI		-0.0062	Neutral
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs727503453; hg19: chr15-43910286;