NM_144672.4:c.-4-93_-4-90dupATAT

Variant names:

• chr16-21678407-C-CATAT
• rs113757042
• NM_144672.4:c.-4-93_-4-90dupATAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_144672.4(OTOA):​c.-4-93_-4-90dupATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0097 in 648,404 control chromosomes in the GnomAD database, including 34 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.010 (13 hom., cov: 25)
  • Exomes 𝑓: 0.0096 (21 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0101 (1508/149068) while in subpopulation NFE AF= 0.0154 (1038/67312). AF 95% confidence interval is 0.0146. There are 13 homozygotes in gnomad4. There are 721 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOA	NM_144672.4	c.-4-93_-4-90dupATAT		intron_variant	Intron 1 of 28	ENST00000646100.2	NP_653273.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2	c.-4-104_-4-103insATAT		intron_variant	Intron 1 of 28		NM_144672.4	ENSP00000496564.2
OTOA	ENST00000647277.1	n.-4-104_-4-103insATAT		intron_variant	Intron 1 of 28			ENSP00000495594.1
OTOA	ENST00000388958.8	c.-108_-107insATAT		upstream_gene_variant		1		ENSP00000373610.3
OTOA	ENST00000286149.8	c.-108_-107insATAT		upstream_gene_variant		5		ENSP00000286149.4

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1507 AN: 148986 Hom.: 13 Cov.: 25

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.00661

Gnomad AMR AF: 0.00479

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.0195

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.0107

GnomAD4 exome AF: 0.00958 AC: 4784 AN: 499336 Hom.: 21 AF XY: 0.0101 AC XY: 2667 AN XY: 263496

Gnomad4 AFR exome AF: 0.00348

Gnomad4 AMR exome AF: 0.00460

Gnomad4 ASJ exome AF: 0.0172

Gnomad4 EAS exome AF: 0.00342

Gnomad4 SAS exome AF: 0.00847

Gnomad4 FIN exome AF: 0.00739

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.0101 AC: 1508 AN: 149068 Hom.: 13 Cov.: 25 AF XY: 0.00992 AC XY: 721 AN XY: 72674

Gnomad4 AFR AF: 0.00306

Gnomad4 AMR AF: 0.00478

Gnomad4 ASJ AF: 0.0237

Gnomad4 EAS AF: 0.00177

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0154

Gnomad4 OTH AF: 0.0106

ClinVar

Not reported in ClinVar

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;