16-21678407-C-CAT

Position:

• chr16-21678407-C-CAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_144672.4(OTOA):​c.-4-91_-4-90dupAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 639,078 control chromosomes in the GnomAD database, including 4,695 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3835 hom., cov: 25)
  • Exomes 𝑓: 0.075 (860 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.100

Genes affected

OTOA (HGNC:16378): (otoancorin) The protein encoded by this gene is specifically expressed in the inner ear, and is located at the interface between the apical surface of the inner ear sensory epithelia and their overlying acellular gels. It is prposed that this protein is involved in the attachment of the inner ear acellular gels to the apical surface of the underlying nonsensory cells. Mutations in this gene are associated with autosomal recessive deafness type 22 (DFNB22). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-21678407-C-CAT is Benign according to our data. Variant chr16-21678407-C-CAT is described in ClinVar as [Benign]. Clinvar id is 1238600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOA	NM_144672.4	c.-4-91_-4-90dupAT		intron_variant		ENST00000646100.2	NP_653273.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2	c.-4-91_-4-90dupAT		intron_variant			NM_144672.4	ENSP00000496564.2
OTOA	ENST00000647277.1	n.-4-91_-4-90dupAT		intron_variant				ENSP00000495594.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 26629 AN: 148852 Hom.: 3829 Cov.: 25

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.0474

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.0543

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.0749 AC: 36704 AN: 490144 Hom.: 860 AF XY: 0.0750 AC XY: 19377 AN XY: 258518

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.0793

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.0647

Gnomad4 FIN exome AF: 0.0508

Gnomad4 NFE exome AF: 0.0580

Gnomad4 OTH exome AF: 0.0913

GnomAD4 genome AF: 0.179 AC: 26668 AN: 148934 Hom.: 3835 Cov.: 25 AF XY: 0.178 AC XY: 12925 AN XY: 72620

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0992

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.0986

Gnomad4 FIN AF: 0.0543

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.157

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113757042; hg19: chr16-21689728;