Variant 6-110358146-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001123364.3(METTL24):c.127C>G(p.Arg43Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000667 in 1,169,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

METTL24
NM_001123364.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.148

Variant links:

Genes affected

METTL24 (HGNC:21566): (methyltransferase like 24) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

METTL24 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06345174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL24	NM_001123364.3 linkuse as main transcript	c.127C>G	p.Arg43Gly	missense_variant	1/5	ENST00000338882.5
METTL24	NM_001354594.2 linkuse as main transcript	c.-325C>G		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL24	ENST00000338882.5 linkuse as main transcript	c.127C>G	p.Arg43Gly	missense_variant	1/5	5	NM_001123364.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000202

AC:

AN:

148180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000450

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000735

AC:

AN:

1021098

Hom.:

Cov.:

AF XY:

0.0000786

AC XY:

AN XY:

483392

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000470

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000574

Gnomad4 NFE exome

AF:

0.0000804

Gnomad4 OTH exome

AF:

0.0000515

GnomAD4 genome

AF:

0.0000202

AC:

AN:

148180

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72214

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000450

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

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

May 17, 2023

The c.127C>G (p.R43G) alteration is located in exon 1 (coding exon 1) of the METTL24 gene. This alteration results from a C to G substitution at nucleotide position 127, causing the arginine (R) at amino acid position 43 to be replaced by a glycine (G). 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

0.057

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.4

DANN

Benign

0.26

DEOGEN2

Benign

0.0047

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.90

REVEL

Benign

0.026

Sift

Benign

0.33

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.063

MutPred

0.20

Gain of relative solvent accessibility (P = 0.005);

MVP

0.055

MPC

0.23

ClinPred

0.067

GERP RS

-3.1

Varity_R

0.064

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

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