rs766464173

Variant names:

• chr7-128480690-C-A
• rs766464173
• NM_018396.3:c.602C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-128480690-C-A
• chr7-128480690-C-T

Variant summary

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

The NM_018396.3(METTL2B):​c.602C>A​(p.Thr201Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,910 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T201M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: METTL2B NM_018396.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.602C>A	p.Thr201Lys	missense	Exon 4 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.602C>A	p.Thr201Lys	missense	Exon 4 of 9	ENSP00000262432.9	Q6P1Q9-1
	METTL2B	ENST00000482555.5	TSL:1	n.845C>A		non_coding_transcript_exon	Exon 3 of 8
	METTL2B	ENST00000930216.1		c.602C>A	p.Thr201Lys	missense	Exon 4 of 10	ENSP00000600275.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453910 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723088

African (AFR) AF: 0.00 AC: 0 AN: 32854

American (AMR) AF: 0.0000236 AC: 1 AN: 42386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25860

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 84606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109482

Other (OTH) AF: 0.00 AC: 0 AN: 59996

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0080	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.21
Sift	Benign	0.076	T
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.77
MutPred		0.64		Gain of ubiquitination at T201 (P = 0.0276)
MVP		0.41
MPC		2.3
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.49
gMVP		0.79
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs766464173; hg19: chr7-128120744;