rs199814237

Variant names:

• chr7-128479389-C-G
• NM_018396.3:c.434C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-128479389-C-G
• chr7-128479389-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018396.3(METTL2B):​c.434C>G​(p.Ser145Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S145L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: METTL2B NM_018396.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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

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=0.06409475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
METTL2B	NM_018396.3	c.434C>G	p.Ser145Trp	missense_variant	Exon 3 of 9	ENST00000262432.13	NP_060866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
METTL2B	ENST00000262432.13	c.434C>G	p.Ser145Trp	missense_variant	Exon 3 of 9	1	NM_018396.3	ENSP00000262432.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.0021	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.024	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.15
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.036	D;D
Polyphen		0.010	B;B
Vest4		0.28
MutPred		0.29		Loss of disorder (P = 0.0759);.;
MVP		0.23
MPC		1.5
ClinPred		0.056	T
GERP RS		-2.5
Varity_R		0.060
gMVP		0.45

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: chr7-128119443;