X-101041342-C-T

Position:

• chrX-101041342-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024917.6(TRMT2B):​c.278G>A​(p.Arg93Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TRMT2B NM_024917.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.28

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]

TRMT2B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27309847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT2B	NM_024917.6	c.278G>A	p.Arg93Lys	missense_variant	4/14	ENST00000372936.4	NP_079193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT2B	ENST00000372936.4	c.278G>A	p.Arg93Lys	missense_variant	4/14	1	NM_024917.6	ENSP00000362027.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.278G>A (p.R93K) alteration is located in exon 4 (coding exon 2) of the TRMT2B gene. This alteration results from a G to A substitution at nucleotide position 278, causing the arginine (R) at amino acid position 93 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.;T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T;.;.
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L;L;L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.32	T;T;T;T
Sift4G	Benign	0.37	T;T;T;T
Polyphen		0.049	B;D;B;B
Vest4		0.45
MutPred		0.64		Gain of methylation at R93 (P = 0.0261);Gain of methylation at R93 (P = 0.0261);Gain of methylation at R93 (P = 0.0261);Gain of methylation at R93 (P = 0.0261);
MVP		0.47
MPC		0.94
ClinPred		0.93	D
GERP RS		4.4
Varity_R		0.36
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100296331;