Variant 11-72105937-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001145309.4(LRTOMT):c.85G>A(p.Ala29Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,385,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRTOMT
NM_001145309.4 missense, splice_region

Scores

Splicing: ADA: 0.00003098

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.325

Variant links:

Genes affected

LRTOMT (HGNC:):

LRTOMT links:

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04451868).

BP6

Variant 11-72105937-G-A is Benign according to our data. Variant chr11-72105937-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3292134.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRTOMT	NM_001145309.4 linkuse as main transcript	c.85G>A	p.Ala29Thr	missense_variant, splice_region_variant	7/9		NP_001138781.1
TOMT	NM_001393500.2 linkuse as main transcript	c.-15G>A		5_prime_UTR_variant	1/3	ENST00000541899.3	NP_001380429.1
LRTOMT	NM_001145308.5 linkuse as main transcript	c.85G>A	p.Ala29Thr	missense_variant, splice_region_variant	5/7		NP_001138780.1
LRTOMT	NM_001145310.4 linkuse as main transcript	c.84-119G>A		intron_variant			NP_001138782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOMT	ENST00000541899.3 linkuse as main transcript	c.-15G>A		5_prime_UTR_variant	1/3	5	NM_001393500.2	ENSP00000494667	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000659

AC:

AN:

151676

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80506

show subpopulations

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 SAS exome

AF:

0.0000440

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1385366

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

680530

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000362

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

4.1

DANN

Benign

0.63

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.28

T;.

M_CAP

Benign

0.046

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.18

Sift

Benign

0.40

T;T

Sift4G

Uncertain

0.042

D;D

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.27

Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);

MVP

0.42

MPC

0.061

ClinPred

0.057

GERP RS

0.91

Varity_R

0.022

gMVP

0.089

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

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