16-21678407-CAT-C

Variant names:

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

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_-4-90delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 630,356 control chromosomes in the GnomAD database, including 419 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (75 hom., cov: 25)
  • Exomes 𝑓: 0.042 (344 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.872
• 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, 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-21678407-CAT-C is Benign according to our data. Variant chr16-21678407-CAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1207013.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOA	NM_144672.4	c.-4-91_-4-90delAT		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.-4-103_-4-102delAT		intron_variant	Intron 1 of 28		NM_144672.4	ENSP00000496564.2
OTOA	ENST00000647277.1	n.-4-103_-4-102delAT		intron_variant	Intron 1 of 28			ENSP00000495594.1
OTOA	ENST00000388958.8	c.-107_-106delAT		upstream_gene_variant		1		ENSP00000373610.3
OTOA	ENST00000286149.8	c.-107_-106delAT		upstream_gene_variant		5		ENSP00000286149.4

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4003 AN: 148962 Hom.: 75 Cov.: 25

Gnomad AFR AF: 0.00703

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0258

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00953

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0418 AC: 20124 AN: 481312 Hom.: 344 AF XY: 0.0410 AC XY: 10404 AN XY: 253454

African (AFR) AF: 0.0123 AC: 126 AN: 10216

American (AMR) AF: 0.0396 AC: 562 AN: 14204

Ashkenazi Jewish (ASJ) AF: 0.0396 AC: 542 AN: 13700

East Asian (EAS) AF: 0.00538 AC: 106 AN: 19698

South Asian (SAS) AF: 0.0197 AC: 695 AN: 35232

European-Finnish (FIN) AF: 0.0475 AC: 1447 AN: 30476

Middle Eastern (MID) AF: 0.0737 AC: 132 AN: 1790

European-Non Finnish (NFE) AF: 0.0466 AC: 15486 AN: 332048

Other (OTH) AF: 0.0429 AC: 1028 AN: 23948

GnomAD4 genome AF: 0.0269 AC: 4004 AN: 149044 Hom.: 75 Cov.: 25 AF XY: 0.0273 AC XY: 1985 AN XY: 72666

African (AFR) AF: 0.00701 AC: 284 AN: 40508

American (AMR) AF: 0.0314 AC: 465 AN: 14832

Ashkenazi Jewish (ASJ) AF: 0.0258 AC: 89 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00975 AC: 46 AN: 4718

European-Finnish (FIN) AF: 0.0373 AC: 368 AN: 9872

Middle Eastern (MID) AF: 0.0739 AC: 21 AN: 284

European-Non Finnish (NFE) AF: 0.0393 AC: 2645 AN: 67302

Other (OTH) AF: 0.0332 AC: 69 AN: 2078

Alfa AF: 0.00906 Hom.: 5

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 04, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.87

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;