7-128477139-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000262432.13(METTL2B):​c.168G>T​(p.Glu56Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

METTL2B
ENST00000262432.13 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33717564).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
METTL2BNM_018396.3 linkuse as main transcriptc.168G>T p.Glu56Asp missense_variant 2/9 ENST00000262432.13 NP_060866.2 Q6P1Q9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
METTL2BENST00000262432.13 linkuse as main transcriptc.168G>T p.Glu56Asp missense_variant 2/91 NM_018396.3 ENSP00000262432.9 Q6P1Q9-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsJan 19, 2024The c.168G>T (p.E56D) alteration is located in exon 2 (coding exon 2) of the METTL2B gene. This alteration results from a G to T substitution at nucleotide position 168, causing the glutamic acid (E) at amino acid position 56 to be replaced by an aspartic acid (D). 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
0.16
BayesDel_addAF
Uncertain
0.037
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T
Eigen
Uncertain
0.26
Eigen_PC
Benign
0.12
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.34
T
MetaSVM
Uncertain
0.21
D
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-2.5
D
REVEL
Uncertain
0.45
Sift
Benign
0.049
D
Sift4G
Benign
0.15
T
Polyphen
0.98
D
Vest4
0.35
MutPred
0.23
Loss of loop (P = 0.1242);
MVP
0.76
MPC
2.0
ClinPred
0.91
D
GERP RS
2.6
Varity_R
0.53
gMVP
0.23

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.

Other links and lift over

dbSNP: rs1799811905; hg19: chr7-128117193; API