16-21678452-G-GTA

Position:

• chr16-21678452-G-GTA

Variant summary

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

The NM_144672.4(OTOA):​c.-4-58_-4-57insAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 984,452 control chromosomes in the GnomAD database, including 688 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (443 hom., cov: 30)
  • Exomes 𝑓: 0.017 (245 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.214

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 16-21678452-G-GTA is Benign according to our data. Variant chr16-21678452-G-GTA is described in ClinVar as [Benign]. Clinvar id is 1236082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOA	NM_144672.4	c.-4-58_-4-57insAT		intron_variant		ENST00000646100.2	NP_653273.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2	c.-4-58_-4-57insAT		intron_variant			NM_144672.4	ENSP00000496564	P2
OTOA	ENST00000647277.1	c.-4-58_-4-57insAT		intron_variant, NMD_transcript_variant				ENSP00000495594

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7379 AN: 150986 Hom.: 440 Cov.: 30

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.0492

Gnomad FIN AF: 0.00932

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.00933

Gnomad OTH AF: 0.0553

GnomAD4 exome AF: 0.0174 AC: 14496 AN: 833390 Hom.: 245 AF XY: 0.0176 AC XY: 7606 AN XY: 433094

Gnomad4 AFR exome AF: 0.0371

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.0196

Gnomad4 FIN exome AF: 0.00777

Gnomad4 NFE exome AF: 0.00436

Gnomad4 OTH exome AF: 0.0202

GnomAD4 genome AF: 0.0489 AC: 7386 AN: 151062 Hom.: 443 Cov.: 30 AF XY: 0.0508 AC XY: 3749 AN XY: 73744

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.00932

Gnomad4 NFE AF: 0.00932

Gnomad4 OTH AF: 0.0538

Alfa AF: 0.00409 Hom.: 0

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

Aug 21, 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: rs144912719; hg19: chr16-21689773;