Variant rs137853187 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_001393500.2(TOMT):c.229G>A(p.Glu77Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,513,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TOMT
NM_001393500.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.84

Variant links:

Genes affected

TOMT (HGNC:55527): (transmembrane O-methyltransferase) This gene encodes a catechol-O-methyltransferase that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to a hydroxyl group of catechols and is essential for auditory and vestibular function. Mutations in this gene have been associated with nonsyndromic deafness. Readthrough transcription is observed across this gene and the adjacent leucine-rich repeat containing 51 gene. A third locus (GeneID:220074) is defined to represent the readthrough transcripts. [provided by RefSeq, Feb 2021]

TOMT links:

LRTOMT (HGNC:):

LRTOMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 11-72106180-G-A is Pathogenic according to our data. Variant chr11-72106180-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 545.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-72106180-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TOMT	NM_001393500.2 linkuse as main transcript	c.229G>A	p.Glu77Lys	missense_variant	1/3	ENST00000541899.3
LRTOMT	NM_001145309.4 linkuse as main transcript	c.328G>A	p.Glu110Lys	missense_variant	7/9
LRTOMT	NM_001145308.5 linkuse as main transcript	c.328G>A	p.Glu110Lys	missense_variant	5/7
LRTOMT	NM_001145310.4 linkuse as main transcript	c.208G>A	p.Glu70Lys	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMT	ENST00000541899.3 linkuse as main transcript	c.229G>A	p.Glu77Lys	missense_variant	1/3	5	NM_001393500.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

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

GnomAD3 exomes

AF:

0.0000362

AC:

AN:

138054

Hom.:

AF XY:

0.0000273

AC XY:

AN XY:

73276

show subpopulations

Gnomad AFR exome

AF:

0.000259

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000365

Gnomad OTH exome

AF:

0.000248

GnomAD4 exome

AF:

0.0000140

AC:

AN:

1361370

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

666442

show subpopulations

Gnomad4 AFR exome

AF:

0.0000964

Gnomad4 AMR exome

AF:

0.0000288

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.0000262

Gnomad4 NFE exome

AF:

0.0000113

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

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

Alfa

AF:

0.000199

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000394

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 63

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.28

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.35

T;T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

D;.;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

1.0

A;A;A;A

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.3

D;D;.

REVEL

Pathogenic

0.69

Sift

Uncertain

0.021

D;D;.

Sift4G

Uncertain

0.016

D;D;.

Polyphen

1.0

D;D;.

Vest4

0.91

MutPred

0.62

Gain of methylation at E110 (P = 0.0148);Gain of methylation at E110 (P = 0.0148);.;

MVP

0.90

MPC

0.41

ClinPred

0.49

GERP RS

4.6

Varity_R

0.55

gMVP

0.80

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over