NM_024917.6:c.365A>G

Variant names:

• chrX-101037990-T-C
• rs1326246962
• NM_024917.6:c.365A>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.365A>G​(p.Asn122Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,206,176 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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 0.000018 (0 hom., 1 hem., cov: 21)
  • Exomes 𝑓: 0.000022 (0 hom. 5 hem.)
• Consequence: TRMT2B NM_024917.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.512
• Publications: 0 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=0.06509146).
• BS2: High Hemizygotes in GnomAdExome4 at 5 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.365A>G	p.Asn122Ser	missense	Exon 5 of 14	NP_079193.2
	TRMT2B	NM_001167970.2		c.365A>G	p.Asn122Ser	missense	Exon 5 of 14	NP_001161442.1	Q96GJ1-1
	TRMT2B	NM_001167972.2		c.365A>G	p.Asn122Ser	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.365A>G	p.Asn122Ser	missense	Exon 5 of 14	ENSP00000362027.3	Q96GJ1-1
	TRMT2B	ENST00000372935.5	TSL:1	c.365A>G	p.Asn122Ser	missense	Exon 5 of 14	ENSP00000362026.1	Q96GJ1-1
	TRMT2B	ENST00000545398.5	TSL:1	c.365A>G	p.Asn122Ser	missense	Exon 4 of 13	ENSP00000438134.1	Q96GJ1-1

Frequencies

GnomAD3 genomes AF: 0.0000181 AC: 2 AN: 110791 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

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: 0.0000377

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183405 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 24 AN: 1095385 Hom.: 0 Cov.: 28 AF XY: 0.0000139 AC XY: 5 AN XY: 360781

African (AFR) AF: 0.00 AC: 0 AN: 26346

American (AMR) AF: 0.00 AC: 0 AN: 35191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19367

East Asian (EAS) AF: 0.00 AC: 0 AN: 30186

South Asian (SAS) AF: 0.0000925 AC: 5 AN: 54059

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.0000214 AC: 18 AN: 839593

Other (OTH) AF: 0.0000217 AC: 1 AN: 45996

GnomAD4 genome AF: 0.0000181 AC: 2 AN: 110791 Hom.: 0 Cov.: 21 AF XY: 0.0000303 AC XY: 1 AN XY: 32975

African (AFR) AF: 0.00 AC: 0 AN: 30495

American (AMR) AF: 0.00 AC: 0 AN: 10200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2636

East Asian (EAS) AF: 0.00 AC: 0 AN: 3540

South Asian (SAS) AF: 0.00 AC: 0 AN: 2595

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5913

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

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 52992

Other (OTH) AF: 0.00 AC: 0 AN: 1505

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.077
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.85
DEOGEN2	Benign	0.045	T
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.51
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.023
Sift	Benign	0.27	T
Sift4G	Benign	0.19	T
Polyphen		0.0060	B
Vest4		0.054
MutPred		0.30		Gain of disorder (P = 0.173)
MVP		0.57
MPC		0.25
ClinPred		0.016	T
GERP RS		0.11
Varity_R		0.049
gMVP		0.21
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1326246962; hg19: chrX-100292979;