chrX-101038014-A-C

Variant names:

• chrX-101038014-A-C
• rs201360816
• NM_024917.6:c.341T>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_024917.6(TRMT2B):​c.341T>G​(p.Leu114Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000928 in 1,207,189 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 1 hem., cov: 21)
  • Exomes 𝑓: 0.000089 (0 hom. 35 hem.)
• Consequence: TRMT2B NM_024917.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1740064).
• BS2: High Hemizygotes in GnomAdExome4 at 35 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.341T>G	p.Leu114Arg	missense	Exon 5 of 14	NP_079193.2
	TRMT2B	NM_001167970.2		c.341T>G	p.Leu114Arg	missense	Exon 5 of 14	NP_001161442.1	Q96GJ1-1
	TRMT2B	NM_001167972.2		c.341T>G	p.Leu114Arg	missense	Exon 4 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.341T>G	p.Leu114Arg	missense	Exon 5 of 14	ENSP00000362027.3	Q96GJ1-1
	TRMT2B	ENST00000372935.5	TSL:1	c.341T>G	p.Leu114Arg	missense	Exon 5 of 14	ENSP00000362026.1	Q96GJ1-1
	TRMT2B	ENST00000545398.5	TSL:1	c.341T>G	p.Leu114Arg	missense	Exon 4 of 13	ENSP00000438134.1	Q96GJ1-1

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 14 AN: 110881 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00493

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000159 AC: 29 AN: 182671 AF XY: 0.000164

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00335

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000489

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000894 AC: 98 AN: 1096308 Hom.: 0 Cov.: 29 AF XY: 0.0000968 AC XY: 35 AN XY: 361688

African (AFR) AF: 0.00 AC: 0 AN: 26354

American (AMR) AF: 0.00 AC: 0 AN: 35107

Ashkenazi Jewish (ASJ) AF: 0.00387 AC: 75 AN: 19366

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.00 AC: 0 AN: 53980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40510

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

European-Non Finnish (NFE) AF: 0.0000167 AC: 14 AN: 840649

Other (OTH) AF: 0.000196 AC: 9 AN: 46024

GnomAD4 genome AF: 0.000126 AC: 14 AN: 110881 Hom.: 0 Cov.: 21 AF XY: 0.0000302 AC XY: 1 AN XY: 33073

African (AFR) AF: 0.00 AC: 0 AN: 30521

American (AMR) AF: 0.00 AC: 0 AN: 10216

Ashkenazi Jewish (ASJ) AF: 0.00493 AC: 13 AN: 2639

East Asian (EAS) AF: 0.00 AC: 0 AN: 3529

South Asian (SAS) AF: 0.00 AC: 0 AN: 2622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5903

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 53033

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

Alfa AF: 0.000347 Hom.: 2

Bravo AF: 0.0000945

ExAC AF: 0.000173 AC: 21

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	Uncertain	0.43
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.5
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.29
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.58		Loss of stability (P = 0.0596)
MVP		0.43
MPC		1.2
ClinPred		0.35	T
GERP RS		3.3
Varity_R		0.78
gMVP		0.92
Mutation Taster		=100/0	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: rs201360816; hg19: chrX-100293003;