rs1326246962

Variant names:

• chrX-101037990-T-A
• rs1326246962
• NM_024917.6:c.365A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-101037990-T-A
• chrX-101037990-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_024917.6(TRMT2B):​c.365A>T​(p.Asn122Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,385 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000027 (0 hom. 2 hem.)
• Consequence: TRMT2B NM_024917.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12273979).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT2B	NM_024917.6	c.365A>T	p.Asn122Ile	missense_variant	Exon 5 of 14	ENST00000372936.4	NP_079193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT2B	ENST00000372936.4	c.365A>T	p.Asn122Ile	missense_variant	Exon 5 of 14	1	NM_024917.6	ENSP00000362027.3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1095385 Hom.: 0 Cov.: 28 AF XY: 0.00000554 AC XY: 2 AN XY: 360781

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000357

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T;T;T
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.56	T;.;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.051
Sift	Benign	0.036	D;D;D
Sift4G	Uncertain	0.031	D;D;D
Polyphen		0.073	B;B;B
Vest4		0.18
MutPred		0.44		Loss of glycosylation at T127 (P = 0.1185);Loss of glycosylation at T127 (P = 0.1185);Loss of glycosylation at T127 (P = 0.1185);
MVP		0.57
MPC		0.41
ClinPred		0.12	T
GERP RS		0.11
Varity_R		0.23
gMVP		0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs1326246962; hg19: chrX-100292979;