rs11114416

Variant names:

• chr12-80367631-G-A
• rs11114416
• NM_001378609.3:c.6402G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-80367631-G-A
• chr12-80367631-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001378609.3(OTOGL):​c.6402G>A​(p.Leu2134Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000361 in 1,384,856 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: 31)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: OTOGL NM_001378609.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 84B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=1.51 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.6402G>A	p.Leu2134Leu	synonymous_variant	Exon 54 of 59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.6402G>A	p.Leu2134Leu	synonymous_variant	Exon 54 of 59	5	NM_001378609.3	ENSP00000447211.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 182930 AF XY: 0.0000205

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 FIN exome AF: 0.0000524

Gnomad NFE exome AF: 0.0000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000361 AC: 5 AN: 1384856 Hom.: 0 Cov.: 29 AF XY: 0.00000437 AC XY: 3 AN XY: 687190

African (AFR) AF: 0.00 AC: 0 AN: 30678

American (AMR) AF: 0.00 AC: 0 AN: 36030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24416

East Asian (EAS) AF: 0.00 AC: 0 AN: 37602

South Asian (SAS) AF: 0.00 AC: 0 AN: 78326

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5570

European-Non Finnish (NFE) AF: 0.00000282 AC: 3 AN: 1063166

Other (OTH) AF: 0.0000174 AC: 1 AN: 57506

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.3
DANN	Benign	0.56
PhyloP100		1.5
PromoterAI		-0.0025	Neutral

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

Other links and lift over

dbSNP: rs11114416; hg19: chr12-80761411;