16-21678407-CAT-C

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_-4-90del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 630,356 control chromosomes in the GnomAD database, including 419 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (75 hom., cov: 25)
  • Exomes 𝑓: 0.042 (344 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.872

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-CAT-C is Benign according to our data. Variant chr16-21678407-CAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1207013.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0635 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOA	ENST00000646100.2	c.-4-91_-4-90del		intron_variant			NM_144672.4	P2
OTOA	ENST00000647277.1	c.-4-91_-4-90del		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4003 AN: 148962 Hom.: 75 Cov.: 25

Gnomad AFR AF: 0.00703

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0258

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00953

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0418 AC: 20124 AN: 481312 Hom.: 344 AF XY: 0.0410 AC XY: 10404 AN XY: 253454

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.0396

Gnomad4 EAS exome AF: 0.00538

Gnomad4 SAS exome AF: 0.0197

Gnomad4 FIN exome AF: 0.0475

Gnomad4 NFE exome AF: 0.0466

Gnomad4 OTH exome AF: 0.0429

GnomAD4 genome AF: 0.0269 AC: 4004 AN: 149044 Hom.: 75 Cov.: 25 AF XY: 0.0273 AC XY: 1985 AN XY: 72666

Gnomad4 AFR AF: 0.00701

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.0258

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00975

Gnomad4 FIN AF: 0.0373

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.00906 Hom.: 5

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 04, 2019

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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;