16-21678407-CATAT-CATATAT

Variant names:

• chr16-21678407-C-CAT
• rs113757042
• NM_144672.4:c.-4-91_-4-90dupAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_144672.4(OTOA):​c.-4-91_-4-90dupAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 639,078 control chromosomes in the GnomAD database, including 4,695 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3835 hom., cov: 25)
  • Exomes 𝑓: 0.075 (860 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 16-21678407-C-CAT is Benign according to our data. Variant chr16-21678407-C-CAT is described in ClinVar as Benign. ClinVar VariationId is 1238600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

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.-4-91_-4-90dupAT		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_-4-103insAT		intron	N/A	ENSP00000496564.2	Q7RTW8-5
	OTOA	ENST00000647277.1		n.-4-104_-4-103insAT		intron	N/A	ENSP00000495594.1	A0A2R8YG28
	OTOA	ENST00000388958.8	TSL:1	c.-108_-107insAT		upstream_gene	N/A	ENSP00000373610.3	Q7RTW8-5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 26629 AN: 148852 Hom.: 3829 Cov.: 25

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.0474

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.0543

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.0749 AC: 36704 AN: 490144 Hom.: 860 AF XY: 0.0750 AC XY: 19377 AN XY: 258518

African (AFR) AF: 0.281 AC: 2864 AN: 10198

American (AMR) AF: 0.137 AC: 1972 AN: 14372

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 1113 AN: 14034

East Asian (EAS) AF: 0.246 AC: 4820 AN: 19614

South Asian (SAS) AF: 0.0647 AC: 2333 AN: 36080

European-Finnish (FIN) AF: 0.0508 AC: 1590 AN: 31302

Middle Eastern (MID) AF: 0.0850 AC: 155 AN: 1824

European-Non Finnish (NFE) AF: 0.0580 AC: 19628 AN: 338312

Other (OTH) AF: 0.0913 AC: 2229 AN: 24408

GnomAD4 genome AF: 0.179 AC: 26668 AN: 148934 Hom.: 3835 Cov.: 25 AF XY: 0.178 AC XY: 12925 AN XY: 72620

African (AFR) AF: 0.383 AC: 15495 AN: 40438

American (AMR) AF: 0.193 AC: 2853 AN: 14816

Ashkenazi Jewish (ASJ) AF: 0.0992 AC: 343 AN: 3456

East Asian (EAS) AF: 0.325 AC: 1651 AN: 5074

South Asian (SAS) AF: 0.0986 AC: 465 AN: 4714

European-Finnish (FIN) AF: 0.0543 AC: 536 AN: 9866

Middle Eastern (MID) AF: 0.106 AC: 30 AN: 284

European-Non Finnish (NFE) AF: 0.0732 AC: 4927 AN: 67302

Other (OTH) AF: 0.157 AC: 325 AN: 2076

Alfa AF: 0.0225 Hom.: 5

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;