rs1132651

Variant names:

• chr7-128500928-T-C
• rs1132651
• NM_018396.3:c.942T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018396.3(METTL2B):​c.942T>C​(p.Tyr314Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,612,724 control chromosomes in the GnomAD database, including 127,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11566 hom., cov: 32)
  • Exomes 𝑓: 0.40 (116296 hom.)
• Consequence: METTL2B NM_018396.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00200
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 7-128500928-T-C is Benign according to our data. Variant chr7-128500928-T-C is described in ClinVar as Benign. ClinVar VariationId is 768200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.002 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

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.942T>C	p.Tyr314Tyr	synonymous	Exon 8 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.942T>C	p.Tyr314Tyr	synonymous	Exon 8 of 9	ENSP00000262432.9	Q6P1Q9-1
	METTL2B	ENST00000482555.5	TSL:1	n.1185T>C		non_coding_transcript_exon	Exon 7 of 8
	METTL2B	ENST00000930216.1		c.1056T>C	p.Tyr352Tyr	synonymous	Exon 9 of 10	ENSP00000600275.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59089 AN: 151886 Hom.: 11567 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.366 AC: 92000 AN: 251384 AF XY: 0.373

Gnomad AFR exome AF: 0.400

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.382

Gnomad EAS exome AF: 0.304

Gnomad FIN exome AF: 0.351

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.397 AC: 579215 AN: 1460720 Hom.: 116296 Cov.: 40 AF XY: 0.397 AC XY: 288503 AN XY: 726728

African (AFR) AF: 0.406 AC: 13576 AN: 33450

American (AMR) AF: 0.258 AC: 11557 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 9976 AN: 26120

East Asian (EAS) AF: 0.299 AC: 11846 AN: 39682

South Asian (SAS) AF: 0.377 AC: 32546 AN: 86226

European-Finnish (FIN) AF: 0.357 AC: 19049 AN: 53412

Middle Eastern (MID) AF: 0.497 AC: 2863 AN: 5766

European-Non Finnish (NFE) AF: 0.409 AC: 454067 AN: 1111006

Other (OTH) AF: 0.393 AC: 23735 AN: 60348

GnomAD4 genome AF: 0.389 AC: 59102 AN: 152004 Hom.: 11566 Cov.: 32 AF XY: 0.386 AC XY: 28684 AN XY: 74302

African (AFR) AF: 0.407 AC: 16882 AN: 41448

American (AMR) AF: 0.319 AC: 4874 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1316 AN: 3472

East Asian (EAS) AF: 0.311 AC: 1609 AN: 5170

South Asian (SAS) AF: 0.377 AC: 1816 AN: 4816

European-Finnish (FIN) AF: 0.361 AC: 3820 AN: 10576

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27411 AN: 67944

Other (OTH) AF: 0.370 AC: 781 AN: 2108

Alfa AF: 0.398 Hom.: 5206

Bravo AF: 0.387

Asia WGS AF: 0.310 AC: 1080 AN: 3478

EpiCase AF: 0.418

EpiControl AF: 0.412

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		-0.0020
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1132651; hg19: chr7-128140982; COSMIC: COSV52307808; COSMIC: COSV52307808;