chr7-128493835-T-A

Variant names:

• chr7-128493835-T-A
• NM_018396.3:c.701T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018396.3(METTL2B):​c.701T>A​(p.Phe234Tyr) 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. 15/22 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: 2.29
• 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]

ENSG00000273184 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07848987).

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.701T>A	p.Phe234Tyr	missense	Exon 6 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.701T>A	p.Phe234Tyr	missense	Exon 6 of 9	ENSP00000262432.9	Q6P1Q9-1
	METTL2B	ENST00000482555.5	TSL:1	n.944T>A		non_coding_transcript_exon	Exon 5 of 8
	METTL2B	ENST00000930216.1		c.701T>A	p.Phe234Tyr	missense	Exon 6 of 10	ENSP00000600275.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.096
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.26
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.060
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.58		Gain of phosphorylation at F234 (P = 0.0944)
MVP		0.37
MPC		1.2
ClinPred		0.13	T
GERP RS		1.9
PromoterAI		-0.0010	Neutral
Varity_R		0.077
gMVP		0.52
Mutation Taster		=87/13	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: chr7-128133889;