rs536538111

Positions:

• chr12-80336990-C-A
• chr12-80336990-C-G
• chr12-80336990-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001378609.3(OTOGL):​c.4846C>A​(p.Arg1616=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000042 in 1,428,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: OTOGL NM_001378609.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.97

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.12).
• BP6: Variant 12-80336990-C-A is Benign according to our data. Variant chr12-80336990-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 227823.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.4846C>A	p.Arg1616=	synonymous_variant	42/59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.4846C>A	p.Arg1616=	synonymous_variant	42/59	5	NM_001378609.3	ENSP00000447211	P1
OTOGL	ENST00000646859.1	c.4711C>A	p.Arg1571=	synonymous_variant	46/63			ENSP00000496036
OTOGL	ENST00000298820.7	c.148C>A	p.Arg50=	synonymous_variant	3/18	5		ENSP00000298820

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000101 AC: 2 AN: 198178 Hom.: 0 AF XY: 0.00000944 AC XY: 1 AN XY: 105916

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000398

Gnomad FIN exome AF: 0.0000514

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000420 AC: 6 AN: 1428240 Hom.: 0 Cov.: 32 AF XY: 0.00000848 AC XY: 6 AN XY: 707470

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000492

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 20, 2016

p.Arg1607Arg in exon 41 of OTOGL: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.12
CADD	Benign	9.1
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs536538111; hg19: chr12-80730770;