rs11300714

chr12-80336781-CTT-Cchr12-80336781-CTT-CTchr12-80336781-CTT-CTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001378609.3(OTOGL):c.4744-6_4744-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,091,336 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OTOGL NM_001378609.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOGL	NM_001378609.3	c.4744-6_4744-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000547103.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOGL	ENST00000547103.7	c.4744-6_4744-5del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001378609.3	P1
OTOGL	ENST00000298820.7	c.45-6_45-5del		splice_polypyrimidine_tract_variant, intron_variant		5
OTOGL	ENST00000646859.1	c.4609-6_4609-5del		splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 147870 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000115 AC: 126 AN: 1091336 Hom.: 0 AF XY: 0.000126 AC XY: 68 AN XY: 540334

Gnomad4 AFR exome AF: 0.0000819

Gnomad4 AMR exome AF: 0.000739

Gnomad4 ASJ exome AF: 0.000101

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000370

Gnomad4 FIN exome AF: 0.0000804

Gnomad4 NFE exome AF: 0.0000794

Gnomad4 OTH exome AF: 0.000153

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 147870 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 71982

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs11300714; hg19: chr12-80730561;