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. The variant received 0 ACMG points: 0P and 0B.

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
• Publications: 2 publications found

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]

OTOA Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 22

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000409 AC: 8 AN: 19560

American (AMR) AF: 0.00103 AC: 34 AN: 33166

Ashkenazi Jewish (ASJ) AF: 0.0000466 AC: 1 AN: 21454

East Asian (EAS) AF: 0.000973 AC: 28 AN: 28788

South Asian (SAS) AF: 0.0000295 AC: 2 AN: 67806

European-Finnish (FIN) AF: 0.0000213 AC: 1 AN: 47018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2932

European-Non Finnish (NFE) AF: 0.0000172 AC: 10 AN: 582262

Other (OTH) AF: 0.0000768 AC: 3 AN: 39080

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.000997 AC: 41 AN: 41140

American (AMR) AF: 0.00133 AC: 20 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000783 AC: 4 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67934

Other (OTH) AF: 0.000476 AC: 1 AN: 2102

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs144912719; hg19: chr16-21689773;