Variant 15-43329316-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014793.5(LCMT2):c.1174C>T(p.Leu392Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

LCMT2
NM_014793.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

LCMT2 (HGNC:17558): (leucine carboxyl methyltransferase 2) The protein encoded by this intronless gene belongs to the highly variable methyltransferase superfamily. This gene is the inferred homolog of the Saccharomyces cerevisiae carboxymethyltransferase gene PPM2 that is essential for the synthesis of the hypermodified guanosine Wybutosine (yW). [provided by RefSeq, Jul 2008]

LCMT2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.079851866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LCMT2	NM_014793.5 linkuse as main transcript	c.1174C>T	p.Leu392Phe	missense_variant	1/1	ENST00000305641.7	NP_055608.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCMT2	ENST00000305641.7 linkuse as main transcript	c.1174C>T	p.Leu392Phe	missense_variant	1/1		NM_014793.5	ENSP00000307214	P1
LCMT2	ENST00000567039.1 linkuse as main transcript	c.*302C>T		3_prime_UTR_variant	2/2	2		ENSP00000457403

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.1174C>T (p.L392F) alteration is located in exon 1 (coding exon 1) of the LCMT2 gene. This alteration results from a C to T substitution at nucleotide position 1174, causing the leucine (L) at amino acid position 392 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.42

M_CAP

Benign

0.028

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.60

D;D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

REVEL

Benign

0.11

Sift

Benign

0.071

Sift4G

Uncertain

0.014

Polyphen

0.0020

Vest4

0.098

MutPred

0.43

Loss of sheet (P = 0.0126);

MVP

0.61

MPC

0.17

ClinPred

0.077

GERP RS

1.4

Varity_R

0.062

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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