chr12-80355759-C-T

Variant names:

• chr12-80355759-C-T
• rs141867785
• NM_001378609.3:c.5617C>T

Variant summary

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

The NM_001378609.3(OTOGL):​c.5617C>T​(p.Pro1873Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,402 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: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: OTOGL NM_001378609.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.46

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 rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3	c.5617C>T	p.Pro1873Ser	missense_variant	Exon 47 of 59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7	c.5617C>T	p.Pro1873Ser	missense_variant	Exon 47 of 59	5	NM_001378609.3	ENSP00000447211.2
OTOGL	ENST00000646859.1	c.5482C>T	p.Pro1828Ser	missense_variant	Exon 51 of 63			ENSP00000496036.1
OTOGL	ENST00000298820.7	c.916C>T	p.Pro306Ser	missense_variant	Exon 8 of 18	5		ENSP00000298820.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461402 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726960

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: 0.0000171

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	T;.;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-7.6	.;.;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	.;.;D
Sift4G	Uncertain	0.0050	.;.;D
Vest4		0.81
MutPred		0.44		.;.;Gain of glycosylation at P1864 (P = 0.0308);
MVP		0.33
MPC		0.070
ClinPred		0.99	D
GERP RS		5.1
gMVP		0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs141867785; hg19: chr12-80749539;