X-101021291-C-A

Position:

• chrX-101021291-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024917.6(TRMT2B):​c.876G>T​(p.Gln292His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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: 1.54

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17775911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT2B	NM_024917.6	c.876G>T	p.Gln292His	missense_variant	10/14	ENST00000372936.4	NP_079193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT2B	ENST00000372936.4	c.876G>T	p.Gln292His	missense_variant	10/14	1	NM_024917.6	ENSP00000362027.3
TRMT2B	ENST00000372935.5	c.876G>T	p.Gln292His	missense_variant	10/14	1		ENSP00000362026.1
TRMT2B	ENST00000545398.5	c.876G>T	p.Gln292His	missense_variant	9/13	1		ENSP00000438134.1
TRMT2B	ENST00000372939.5	c.741G>T	p.Gln247His	missense_variant	10/14	1		ENSP00000362030.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

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

Aug 26, 2022

The c.876G>T (p.Q292H) alteration is located in exon 10 (coding exon 8) of the TRMT2B gene. This alteration results from a G to T substitution at nucleotide position 876, causing the glutamine (Q) at amino acid position 292 to be replaced by a histidine (H). 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	0.20
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T;.;T;T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D;D;.;.
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;.;L;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.066
Sift	Benign	0.095	T;T;T;T
Sift4G	Uncertain	0.052	T;T;T;T
Polyphen		0.18	B;D;B;B
Vest4		0.19
MutPred		0.23		Gain of catalytic residue at Q292 (P = 0.0365);.;Gain of catalytic residue at Q292 (P = 0.0365);Gain of catalytic residue at Q292 (P = 0.0365);
MVP		0.87
MPC		0.29
ClinPred		0.63	D
GERP RS		4.0
Varity_R		0.22
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100276280;