chr16-21678452-G-GTATA

Variant names:

• chr16-21678452-G-GTATA
• rs144912719
• NM_144672.4:c.-4-58_-4-57insATAT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144672.4(OTOA):​c.-4-58_-4-57insATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 993,292 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOA	NM_144672.4	c.-4-58_-4-57insATAT		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.-4-59_-4-58insTATA		intron_variant	Intron 1 of 28		NM_144672.4	ENSP00000496564.2
OTOA	ENST00000647277.1	n.-4-59_-4-58insTATA		intron_variant	Intron 1 of 28			ENSP00000495594.1
OTOA	ENST00000388958.8	c.-63_-62insTATA		upstream_gene_variant		1		ENSP00000373610.3
OTOA	ENST00000286149.8	c.-63_-62insTATA		upstream_gene_variant		5		ENSP00000286149.4

Frequencies

GnomAD3 genomes AF: 0.000443 AC: 67 AN: 151150 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000999

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000781

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.000103 AC: 87 AN: 842066 Hom.: 0 AF XY: 0.000103 AC XY: 45 AN XY: 437608

Gnomad4 AFR exome AF: 0.000409

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.0000466

Gnomad4 EAS exome AF: 0.000973

Gnomad4 SAS exome AF: 0.0000295

Gnomad4 FIN exome AF: 0.0000213

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.0000768

GnomAD4 genome AF: 0.000443 AC: 67 AN: 151226 Hom.: 0 Cov.: 30 AF XY: 0.000339 AC XY: 25 AN XY: 73840

Gnomad4 AFR AF: 0.000997

Gnomad4 AMR AF: 0.00133

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000783

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000476

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: rs144912719; hg19: chr16-21689773;