rs11300714

Variant names:

• chr12-80336781-CTTT-C
• rs11300714
• NM_001378609.3:c.4744-7_4744-5delTTT

Your query was ambiguous. Multiple possible variants found:

• chr12-80336781-CTTT-C
• chr12-80336781-CTTT-CT
• chr12-80336781-CTTT-CTT
• chr12-80336781-CTTT-CTTTT
• chr12-80336781-CTTT-CTTTTT
• chr12-80336781-CTTT-CTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001378609.3(OTOGL):​c.4744-7_4744-5delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,093,614 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: OTOGL NM_001378609.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.4744-7_4744-5delTTT		splice_region_variant, intron_variant	Intron 40 of 58	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.4744-15_4744-13delTTT		intron_variant	Intron 40 of 58	5	NM_001378609.3	ENSP00000447211.2
OTOGL	ENST00000646859.1	c.4609-15_4609-13delTTT		intron_variant	Intron 44 of 62			ENSP00000496036.1
OTOGL	ENST00000298820.7	c.43-15_43-13delTTT		intron_variant	Intron 1 of 17	5		ENSP00000298820.3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.0000269 AC: 2 AN: 74216 AF XY: 0.0000507

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: 0.00

Gnomad NFE exome AF: 0.0000347

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1093614 Hom.: 0 AF XY: 0.00000554 AC XY: 3 AN XY: 541472

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24490

American (AMR) AF: 0.0000350 AC: 1 AN: 28552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19810

East Asian (EAS) AF: 0.00 AC: 0 AN: 26202

South Asian (SAS) AF: 0.0000160 AC: 1 AN: 62402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4040

European-Non Finnish (NFE) AF: 0.00000118 AC: 1 AN: 844906

Other (OTH) AF: 0.00 AC: 0 AN: 45834

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000468493), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs11300714; hg19: chr12-80730561;