chr16-21678583-TAC-T

Position:

• chr16-21678583-TAC-T

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_144672.4(OTOA):​c.71_72del​(p.Thr24SerfsTer43) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OTOA NM_144672.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.585

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 Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 11 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-21678583-TAC-T is Pathogenic according to our data. Variant chr16-21678583-TAC-T is described in ClinVar as [Pathogenic]. Clinvar id is 2800906.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOA	NM_144672.4	c.71_72del	p.Thr24SerfsTer43	frameshift_variant	2/29	ENST00000646100.2	NP_653273.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2	c.71_72del	p.Thr24SerfsTer43	frameshift_variant	2/29		NM_144672.4	ENSP00000496564	P2
OTOA	ENST00000388958.8	c.71_72del	p.Thr24SerfsTer43	frameshift_variant	1/28	1		ENSP00000373610	P2
OTOA	ENST00000286149.8	c.71_72del	p.Thr24SerfsTer43	frameshift_variant	1/28	5		ENSP00000286149	A2
OTOA	ENST00000647277.1	c.71_72del	p.Thr24SerfsTer43	frameshift_variant, NMD_transcript_variant	2/29			ENSP00000495594

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 14, 2023

This sequence change creates a premature translational stop signal (p.Thr24Serfs*43) in the OTOA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTOA are known to be pathogenic (PMID: 11972037). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with OTOA-related conditions. For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-21689904;