Variant 12-82389816-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_032230.3(METTL25):c.425G>A(p.Gly142Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000624 in 1,570,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

METTL25
NM_032230.3 missense, splice_region

Scores

Splicing: ADA: 0.0004367

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0640

Variant links:

Genes affected

METTL25 (HGNC:26228): (methyltransferase like 25) Predicted to enable methyltransferase activity. Predicted to be involved in methylation. [provided by Alliance of Genome Resources, Apr 2022]

METTL25 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=0.0987829).

BP6

Variant 12-82389816-G-A is Benign according to our data. Variant chr12-82389816-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2310782.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
METTL25	NM_032230.3 linkuse as main transcript	c.425G>A	p.Gly142Asp	missense_variant, splice_region_variant	3/12	ENST00000248306.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
METTL25	ENST00000248306.8 linkuse as main transcript	c.425G>A	p.Gly142Asp	missense_variant, splice_region_variant	3/12	1	NM_032230.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151790

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

244318

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

131982

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000360

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000677

AC:

AN:

1418722

Hom.:

Cov.:

AF XY:

0.0000777

AC XY:

AN XY:

707584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000872

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151790

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74122

show subpopulations

Gnomad4 AFR

AF:

0.0000484

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

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

-0.31

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.50

DEOGEN2

Benign

0.0014

T;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.39

N;.

MutationTaster

Benign

0.98

PrimateAI

Benign

0.30

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.030

Sift

Benign

0.51

T;T

Sift4G

Benign

0.75

T;T

Polyphen

0.0

B;.

Vest4

0.13

MutPred

0.37

Gain of catalytic residue at R140 (P = 0.0387);Gain of catalytic residue at R140 (P = 0.0387);

MVP

0.27

MPC

0.017

ClinPred

0.026

GERP RS

-0.77

Varity_R

0.041

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00044

dbscSNV1_RF

Benign

0.15

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