7-128501812-C-G

Position:

• chr7-128501812-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018396.3(METTL2B):​c.1033C>G​(p.Leu345Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: METTL2B NM_018396.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.548

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08438927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
METTL2B	NM_018396.3	c.1033C>G	p.Leu345Val	missense_variant	9/9	ENST00000262432.13	NP_060866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL2B	ENST00000262432.13	c.1033C>G	p.Leu345Val	missense_variant	9/9	1	NM_018396.3	ENSP00000262432	P1
METTL2B	ENST00000482555.5	n.1276C>G		non_coding_transcript_exon_variant	8/8	1
METTL2B	ENST00000480046.5	c.838C>G	p.Leu280Val	missense_variant	8/8	2		ENSP00000418402
METTL2B	ENST00000481392.1	c.325C>G	p.Leu109Val	missense_variant	4/5	3		ENSP00000418989

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.1033C>G (p.L345V) alteration is located in exon 9 (coding exon 9) of the METTL2B gene. This alteration results from a C to G substitution at nucleotide position 1033, causing the leucine (L) at amino acid position 345 to be replaced by a valine (V). 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	0.077
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.017	T;.;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.084	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	0.97	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.019
Sift	Benign	0.069	T;T;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.10
MutPred		0.32		Gain of MoRF binding (P = 0.0919);.;.;
MVP		0.26
MPC		0.082
ClinPred		0.081	T
GERP RS		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.28

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.

Other links and lift over

hg19: chr7-128141866;