chr16-21678407-C-CATAT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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, 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144672.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOA	NM_144672.4	MANE Select	c.-4-93_-4-90dupATAT		intron	N/A	NP_653273.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOA	ENST00000646100.2	MANE Select	c.-4-104_-4-103insATAT		intron	N/A	ENSP00000496564.2	Q7RTW8-5
	OTOA	ENST00000647277.1		n.-4-104_-4-103insATAT		intron	N/A	ENSP00000495594.1	A0A2R8YG28
	OTOA	ENST00000388958.8	TSL:1	c.-108_-107insATAT		upstream_gene	N/A	ENSP00000373610.3	Q7RTW8-5

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

African (AFR) AF: 0.00348 AC: 36 AN: 10344

American (AMR) AF: 0.00460 AC: 68 AN: 14772

Ashkenazi Jewish (ASJ) AF: 0.0172 AC: 246 AN: 14330

East Asian (EAS) AF: 0.00342 AC: 69 AN: 20200

South Asian (SAS) AF: 0.00847 AC: 313 AN: 36954

European-Finnish (FIN) AF: 0.00739 AC: 235 AN: 31800

Middle Eastern (MID) AF: 0.0140 AC: 26 AN: 1860

European-Non Finnish (NFE) AF: 0.0103 AC: 3531 AN: 344210

Other (OTH) AF: 0.0105 AC: 260 AN: 24866

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

African (AFR) AF: 0.00306 AC: 124 AN: 40502

American (AMR) AF: 0.00478 AC: 71 AN: 14842

Ashkenazi Jewish (ASJ) AF: 0.0237 AC: 82 AN: 3456

East Asian (EAS) AF: 0.00177 AC: 9 AN: 5086

South Asian (SAS) AF: 0.0106 AC: 50 AN: 4718

European-Finnish (FIN) AF: 0.0102 AC: 101 AN: 9882

Middle Eastern (MID) AF: 0.0176 AC: 5 AN: 284

European-Non Finnish (NFE) AF: 0.0154 AC: 1038 AN: 67312

Other (OTH) AF: 0.0106 AC: 22 AN: 2078

Alfa AF: 0.00499 Hom.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.10

Splicing

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

Other links and lift over

dbSNP: rs113757042; hg19: chr16-21689728;