Genetic Variant STRC:c.3307-17_3307-16dupAA (chr15-43610999-G-GTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_153700.2(STRC):c.3307-17_3307-16dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000813 in 1,279,084 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00018 ( 1 hom., cov: 23)

Exomes 𝑓: 0.000075 ( 1 hom. )

Consequence

STRC
NM_153700.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.213

Publications

0 publications found

Variant links:

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

STRC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRC	NM_153700.2 link	c.3307-17_3307-16dupAA		intron_variant	Intron 13 of 28	ENST00000450892.7	NP_714544.1	Q7RTU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRC	ENST00000450892.7 link	c.3307-17_3307-16dupAA		intron_variant	Intron 13 of 28	5	NM_153700.2	ENSP00000401513.2		Q7RTU9

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

75776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000122

Gnomad ASJ

AF:

0.000575

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00449

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000244

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000187

AC:

AN:

230240

AF XY:

0.000257

show subpopulations

Gnomad AFR exome

AF:

0.000339

Gnomad AMR exome

AF:

0.0000621

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000292

Gnomad OTH exome

AF:

0.000354

GnomAD4 exome

AF:

0.0000748

AC:

AN:

1203274

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

602336

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

22044

American (AMR)

AF:

0.0000287

AC:

AN:

34876

Ashkenazi Jewish (ASJ)

AF:

0.0000967

AC:

AN:

20688

East Asian (EAS)

AF:

0.0000277

AC:

AN:

36064

South Asian (SAS)

AF:

0.00100

AC:

AN:

70864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50234

Middle Eastern (MID)

AF:

0.000854

AC:

AN:

4682

European-Non Finnish (NFE)

AF:

0.00000657

AC:

AN:

913850

Other (OTH)

AF:

0.000100

AC:

AN:

49972

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.282

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000185

AC:

AN:

75810

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

AN XY:

37676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9824

American (AMR)

AF:

0.000121

AC:

AN:

8236

Ashkenazi Jewish (ASJ)

AF:

0.000575

AC:

AN:

1740

East Asian (EAS)

AF:

0.00

AC:

AN:

3150

South Asian (SAS)

AF:

0.00448

AC:

AN:

2454

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7660

Middle Eastern (MID)

AF:

0.00

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.0000244

AC:

AN:

40938

Other (OTH)

AF:

0.00

AC:

AN:

1090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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15-43610999-GT-GTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over