12-80209639-A-G

Position:

• chr12-80209639-A-G

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+129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 490,608 control chromosomes in the GnomAD database, including 470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (365 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (105 hom.)
• Consequence: OTOGL NM_001378609.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.637

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=-0.84).
• BP6: Variant 12-80209639-A-G is Benign according to our data. Variant chr12-80209639-A-G is described in ClinVar as [Benign]. Clinvar id is 1178823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOGL	NM_001378609.3	c.79+129A>G		intron_variant		ENST00000547103.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOGL	ENST00000547103.7	c.79+129A>G		intron_variant		5	NM_001378609.3	P1
OTOGL	ENST00000646859.1	c.79+129A>G		intron_variant
OTOGL	ENST00000643417.1	n.739+129A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5695 AN: 152120 Hom.: 361 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.00533 AC: 1803 AN: 338370 Hom.: 105 AF XY: 0.00480 AC XY: 834 AN XY: 173920

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.00824

Gnomad4 ASJ exome AF: 0.000378

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000457

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000566

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0376 AC: 5717 AN: 152238 Hom.: 365 Cov.: 32 AF XY: 0.0358 AC XY: 2669 AN XY: 74456

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0302 Hom.: 29

Bravo AF: 0.0433

Asia WGS AF: 0.0110 AC: 39 AN: 3452

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

Dec 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.74

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: rs1244909; hg19: chr12-80603419;