16-21728953-C-T

Variant names:

• chr16-21728953-C-T
• rs8050407
• NM_144672.4:c.2207+522C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144672.4(OTOA):​c.2207+522C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,024 control chromosomes in the GnomAD database, including 4,715 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4715 hom., cov: 31)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 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.2207+522C>T		intron	N/A	NP_653273.3
	OTOA	NM_001161683.2		c.1970+522C>T		intron	N/A	NP_001155155.1	Q7RTW8-4
	OTOA	NM_170664.3		c.1235+522C>T		intron	N/A	NP_733764.1	Q7RTW8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOA	ENST00000646100.2	MANE Select	c.2207+522C>T		intron	N/A	ENSP00000496564.2	Q7RTW8-5
	OTOA	ENST00000388958.8	TSL:1	c.2207+522C>T		intron	N/A	ENSP00000373610.3	Q7RTW8-5
	OTOA	ENST00000286149.8	TSL:5	c.2249+522C>T		intron	N/A	ENSP00000286149.4	Q7RTW8-1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36969 AN: 151906 Hom.: 4714 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 36975 AN: 152024 Hom.: 4715 Cov.: 31 AF XY: 0.238 AC XY: 17714 AN XY: 74302

African (AFR) AF: 0.205 AC: 8511 AN: 41452

American (AMR) AF: 0.255 AC: 3898 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3472

East Asian (EAS) AF: 0.140 AC: 722 AN: 5166

South Asian (SAS) AF: 0.116 AC: 558 AN: 4822

European-Finnish (FIN) AF: 0.267 AC: 2817 AN: 10554

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18519 AN: 67972

Other (OTH) AF: 0.256 AC: 540 AN: 2110

Alfa AF: 0.256 Hom.: 3363

Bravo AF: 0.239

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.73
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs8050407; hg19: chr16-21740274;