rs200215069

chr16-21678953-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BP6_Very_Strong

The NM_144672.4(OTOA):c.120+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 1,613,574 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00043 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (1 hom.)
• Consequence: OTOA NM_144672.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.512

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 16-21678953-C-G is Benign according to our data. Variant chr16-21678953-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 164816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-21678953-C-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOA	NM_144672.4	c.120+10C>G		intron_variant		ENST00000646100.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOA	ENST00000646100.2	c.120+10C>G		intron_variant			NM_144672.4	P2
OTOA	ENST00000388958.8	c.120+10C>G		intron_variant		1		P2
OTOA	ENST00000286149.8	c.120+10C>G		intron_variant		5		A2
OTOA	ENST00000647277.1	c.120+10C>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 65 AN: 152114 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000362 AC: 91 AN: 251356 Hom.: 0 AF XY: 0.000368 AC XY: 50 AN XY: 135856

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000371

Gnomad NFE exome AF: 0.000668

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000500 AC: 730 AN: 1461460 Hom.: 1 Cov.: 33 AF XY: 0.000517 AC XY: 376 AN XY: 727048

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000413

Gnomad4 NFE exome AF: 0.000604

Gnomad4 OTH exome AF: 0.000431

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152114 Hom.: 1 Cov.: 32 AF XY: 0.000458 AC XY: 34 AN XY: 74270

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.000956

Alfa AF: 0.000754 Hom.: 1

Bravo AF: 0.000295

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 30, 2012

120+10C>G in Intron 02 of OTOA: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce and has been identified in 3/7020 European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	9.9
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs200215069; hg19: chr16-21690274;