Variant 12-80353429-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001378609.3(OTOGL):c.5512C>T(p.Leu1838Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,520 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OTOGL
NM_001378609.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.325

Variant links:

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]

OTOGL links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=0.325 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOGL	NM_001378609.3 linkuse as main transcript	c.5512C>T	p.Leu1838Leu	synonymous_variant	46/59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OTOGL	ENST00000547103.7 linkuse as main transcript	c.5512C>T	p.Leu1838Leu	synonymous_variant	46/59	5	NM_001378609.3	ENSP00000447211.2	Q3ZCN5
OTOGL	ENST00000646859.1 linkuse as main transcript	c.5377C>T	p.Leu1793Leu	synonymous_variant	50/63			ENSP00000496036.1	A0A2R8YF04
OTOGL	ENST00000298820.7 linkuse as main transcript	c.811C>T	p.Leu271Leu	synonymous_variant	7/18	5		ENSP00000298820.3	H7BXL6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450520

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720306

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.3

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over