Variant 7-128479173-A-G 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_018396.3(METTL2B):c.218A>G(p.Asn73Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000688 in 1,612,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

METTL2B
NM_018396.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

METTL2B (HGNC:18272): (methyltransferase 2B, tRNA N3-cytidine) This gene is a member of a family of methyltransferases that share homology with, but are distinct from, the UbiE family of methyltransferases. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

METTL2B 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=0.01728496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL2B	NM_018396.3 linkuse as main transcript	c.218A>G	p.Asn73Ser	missense_variant	3/9	ENST00000262432.13	NP_060866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL2B	ENST00000262432.13 linkuse as main transcript	c.218A>G	p.Asn73Ser	missense_variant	3/9	1	NM_018396.3	ENSP00000262432	P1	Q6P1Q9-1
METTL2B	ENST00000482555.5 linkuse as main transcript	n.461A>G		non_coding_transcript_exon_variant	2/8	1
METTL2B	ENST00000480046.5 linkuse as main transcript	c.23A>G	p.Asn8Ser	missense_variant	2/8	2		ENSP00000418402		Q6P1Q9-2
METTL2B	ENST00000497665.5 linkuse as main transcript	c.*31A>G		3_prime_UTR_variant, NMD_transcript_variant	4/8	5		ENSP00000417616

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000149

AC:

AN:

248528

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

135010

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00158

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000569

AC:

AN:

1459864

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

725902

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00129

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000901

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000184

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000959

Hom.:

Bravo

AF:

0.000181

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Aug 19, 2023

The c.218A>G (p.N73S) alteration is located in exon 3 (coding exon 3) of the METTL2B gene. This alteration results from a A to G substitution at nucleotide position 218, causing the asparagine (N) at amino acid position 73 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

0.044

Eigen_PC

Benign

-0.0014

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0032

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

0.71

N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.13

Sift

Benign

0.071

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.46

P;P

Vest4

0.22

MVP

0.28

MPC

1.3

ClinPred

0.060

GERP RS

2.9

Varity_R

0.15

gMVP

0.19

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