Variant 7-128476805-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000262432.13(METTL2B):c.40G>A(p.Ala14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A14D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

METTL2B
ENST00000262432.13 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0770

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:

METTL2B (HGNC:):

METTL2B links:

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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=0.047070056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL2B	NM_018396.3 linkuse as main transcript	c.40G>A	p.Ala14Thr	missense_variant	1/9	ENST00000262432.13	NP_060866.2	Q6P1Q9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL2B	ENST00000262432.13 linkuse as main transcript	c.40G>A	p.Ala14Thr	missense_variant	1/9	1	NM_018396.3	ENSP00000262432.9		Q6P1Q9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727218

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:

0.00000180

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

Mar 15, 2024

The c.40G>A (p.A14T) alteration is located in exon 1 (coding exon 1) of the METTL2B gene. This alteration results from a G to A substitution at nucleotide position 40, causing the alanine (A) at amino acid position 14 to be replaced by a threonine (T). 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

0.075

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.61

M_CAP

Benign

0.038

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.28

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.14

REVEL

Benign

0.16

Sift

Benign

0.61

Sift4G

Benign

0.59

Polyphen

0.0050

Vest4

0.095

MutPred

0.23

Gain of phosphorylation at A14 (P = 0.0241);

MVP

0.19

MPC

0.12

ClinPred

0.075

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.050

gMVP

0.090

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over