12-80209626-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378609.3(OTOGL):c.79+116A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 582,352 control chromosomes in the GnomAD database, including 66,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (14841 hom., cov: 32)
  • Exomes 𝑓: 0.48 (51684 hom.)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.938

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-80209626-A-T is Benign according to our data. Variant chr12-80209626-A-T is described in ClinVar as [Benign]. Clinvar id is 1274148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOGL	NM_001378609.3	c.79+116A>T		intron_variant		ENST00000547103.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOGL	ENST00000547103.7	c.79+116A>T		intron_variant		5	NM_001378609.3	P1
OTOGL	ENST00000646859.1	c.79+116A>T		intron_variant
OTOGL	ENST00000643417.1	n.739+116A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61443 AN: 151910 Hom.: 14837 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.484 AC: 208173 AN: 430320 Hom.: 51684 AF XY: 0.486 AC XY: 109081 AN XY: 224556

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.513

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.469

GnomAD4 genome AF: 0.404 AC: 61454 AN: 152032 Hom.: 14841 Cov.: 32 AF XY: 0.407 AC XY: 30260 AN XY: 74302

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.414

Alfa AF: 0.458 Hom.: 2175

Bravo AF: 0.392

Asia WGS AF: 0.461 AC: 1593 AN: 3450

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.94
Dann	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs4842344; hg19: chr12-80603406; COSMIC: COSV72007592;