chr7-128476806-C-A

Variant names:

• chr7-128476806-C-A
• NM_018396.3:c.41C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018396.3(METTL2B):​c.41C>A​(p.Ala14Asp) 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. 16/22 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. A14T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: METTL2B NM_018396.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.212
• Publications: 0 publications found

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]

ENSG00000302221 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042443186).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018396.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL2B	NM_018396.3	MANE Select	c.41C>A	p.Ala14Asp	missense	Exon 1 of 9	NP_060866.2	Q6P1Q9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL2B	ENST00000262432.13	TSL:1 MANE Select	c.41C>A	p.Ala14Asp	missense	Exon 1 of 9	ENSP00000262432.9	Q6P1Q9-1
	METTL2B	ENST00000482555.5	TSL:1	n.78C>A		non_coding_transcript_exon	Exon 1 of 8
	METTL2B	ENST00000930216.1		c.41C>A	p.Ala14Asp	missense	Exon 1 of 10	ENSP00000600275.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.5
DANN	Benign	0.46
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-0.81	N
PhyloP100		0.21
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.14
Sift	Benign	0.64	T
Sift4G	Benign	0.63	T
Polyphen		0.0	B
Vest4		0.070
MutPred		0.31		Gain of disorder (P = 0.0443)
MVP		0.12
MPC		0.19
ClinPred		0.059	T
GERP RS		-2.2
PromoterAI		0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.18
gMVP		0.16
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr7-128116860;