NM_024917.6:c.449A>G

Variant names:

• chrX-101037063-T-C
• rs758839212
• NM_024917.6:c.449A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024917.6(TRMT2B):​c.449A>G​(p.Asn150Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000398 in 1,205,841 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.000038 (0 hom. 8 hem.)
• Consequence: TRMT2B NM_024917.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0860
• Publications: 2 publications found

Genes affected

TRMT2B (HGNC:25748): (tRNA methyltransferase 2 homolog B) This gene encodes a homolog of the TRM2 gene in S. cerevisiae. The yeast gene encodes a tRNA methyltransferase that plays a role in tRNA maturation. The yeast protein also has endo-exonuclease activity and may be involved in DNA double strand break repair. Alternative splicing results in multiple transcripts encoding different isoforms. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04035732).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024917.6. 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
	TRMT2B	NM_024917.6	MANE Select	c.449A>G	p.Asn150Ser	missense	Exon 6 of 14	NP_079193.2
	TRMT2B	NM_001167970.2		c.449A>G	p.Asn150Ser	missense	Exon 6 of 14	NP_001161442.1	Q96GJ1-1
	TRMT2B	NM_001167972.2		c.449A>G	p.Asn150Ser	missense	Exon 5 of 13	NP_001161444.1	Q96GJ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT2B	ENST00000372936.4	TSL:1 MANE Select	c.449A>G	p.Asn150Ser	missense	Exon 6 of 14	ENSP00000362027.3	Q96GJ1-1
	TRMT2B	ENST00000372935.5	TSL:1	c.449A>G	p.Asn150Ser	missense	Exon 6 of 14	ENSP00000362026.1	Q96GJ1-1
	TRMT2B	ENST00000545398.5	TSL:1	c.449A>G	p.Asn150Ser	missense	Exon 5 of 13	ENSP00000438134.1	Q96GJ1-1

Frequencies

GnomAD3 genomes AF: 0.0000538 AC: 6 AN: 111464 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000978

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000564

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000546 AC: 10 AN: 183236 AF XY: 0.0000443

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.000182

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000384 AC: 42 AN: 1094323 Hom.: 0 Cov.: 28 AF XY: 0.0000222 AC XY: 8 AN XY: 359711

African (AFR) AF: 0.000114 AC: 3 AN: 26333

American (AMR) AF: 0.000170 AC: 6 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19355

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30181

South Asian (SAS) AF: 0.0000555 AC: 3 AN: 54033

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40523

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.0000322 AC: 27 AN: 838585

Other (OTH) AF: 0.0000435 AC: 2 AN: 45983

GnomAD4 genome AF: 0.0000538 AC: 6 AN: 111518 Hom.: 0 Cov.: 22 AF XY: 0.0000593 AC XY: 2 AN XY: 33720

African (AFR) AF: 0.0000976 AC: 3 AN: 30740

American (AMR) AF: 0.00 AC: 0 AN: 10343

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3544

South Asian (SAS) AF: 0.00 AC: 0 AN: 2653

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000564 AC: 3 AN: 53163

Other (OTH) AF: 0.00 AC: 0 AN: 1500

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	0.063
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.94
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N
PhyloP100		-0.086
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.024
Sift	Benign	0.73	T
Sift4G	Benign	0.53	T
Polyphen		0.0050	B
Vest4		0.048
MVP		0.52
MPC		0.24
ClinPred		0.022	T
GERP RS		-0.51
Varity_R		0.024
gMVP		0.22
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs758839212; hg19: chrX-100292052; COSMIC: COSV58618716;