rs1308469405

Variant names:

• chr15-43614438-A-G
• rs1308469405
• NM_153700.2:c.2172T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_153700.2(STRC):​c.2172T>C​(p.Val724Val) 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 0.000015 (0 hom., cov: 7)
  • Exomes 𝑓: 0.0000052 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STRC NM_153700.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.665
• 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: 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 15-43614438-A-G is Benign according to our data. Variant chr15-43614438-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 505236.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.665 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	NM_153700.2	MANE Select	c.2172T>C	p.Val724Val	synonymous	Exon 5 of 29	NP_714544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRC	ENST00000450892.7	TSL:5 MANE Select	c.2172T>C	p.Val724Val	synonymous	Exon 5 of 29	ENSP00000401513.2
	STRC	ENST00000440125.5	TSL:1	n.*174T>C		non_coding_transcript_exon	Exon 6 of 28	ENSP00000394866.1
	ENSG00000284772	ENST00000643290.1		n.*1393T>C		non_coding_transcript_exon	Exon 8 of 9	ENSP00000495476.1

Frequencies

GnomAD3 genomes AF: 0.0000155 AC: 1 AN: 64520 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000158

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 102696 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000517 AC: 3 AN: 580700 Hom.: 0 Cov.: 7 AF XY: 0.00000651 AC XY: 2 AN XY: 307056

African (AFR) AF: 0.00 AC: 0 AN: 6562

American (AMR) AF: 0.00 AC: 0 AN: 29470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14888

East Asian (EAS) AF: 0.0000754 AC: 2 AN: 26518

South Asian (SAS) AF: 0.00 AC: 0 AN: 53616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2166

European-Non Finnish (NFE) AF: 0.00000262 AC: 1 AN: 381934

Other (OTH) AF: 0.00 AC: 0 AN: 27226

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000155 AC: 1 AN: 64520 Hom.: 0 Cov.: 7 AF XY: 0.0000326 AC XY: 1 AN XY: 30640

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

African (AFR) AF: 0.00 AC: 0 AN: 6558

American (AMR) AF: 0.000158 AC: 1 AN: 6330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1646

East Asian (EAS) AF: 0.00 AC: 0 AN: 2344

South Asian (SAS) AF: 0.00 AC: 0 AN: 1638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 39076

Other (OTH) AF: 0.00 AC: 0 AN: 774

⚠️ 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: 0.000253 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.7
DANN	Benign	0.86
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1308469405; hg19: chr15-43906636;