X-101020514-C-T

Variant names:

• chrX-101020514-C-T
• NM_024917.6:c.1141G>A

Variant summary

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

The NM_024917.6(TRMT2B):​c.1141G>A​(p.Asp381Asn) 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. 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: 2.46

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 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=0.35705853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT2B	NM_024917.6	c.1141G>A	p.Asp381Asn	missense_variant	Exon 11 of 14	ENST00000372936.4	NP_079193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT2B	ENST00000372936.4	c.1141G>A	p.Asp381Asn	missense_variant	Exon 11 of 14	1	NM_024917.6	ENSP00000362027.3
TRMT2B	ENST00000372935.5	c.1141G>A	p.Asp381Asn	missense_variant	Exon 11 of 14	1		ENSP00000362026.1
TRMT2B	ENST00000545398.5	c.1141G>A	p.Asp381Asn	missense_variant	Exon 10 of 13	1		ENSP00000438134.1
TRMT2B	ENST00000372939.5	c.1006G>A	p.Asp336Asn	missense_variant	Exon 11 of 14	1		ENSP00000362030.1

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

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1141G>A (p.D381N) alteration is located in exon 11 (coding exon 9) of the TRMT2B gene. This alteration results from a G to A substitution at nucleotide position 1141, causing the aspartic acid (D) at amino acid position 381 to be replaced by an asparagine (N). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.;T;T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;.;.
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;M;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.2	D;D;D;D
REVEL	Benign	0.093
Sift	Benign	0.057	T;T;T;T
Sift4G	Benign	0.067	T;T;T;T
Polyphen		0.75	P;P;P;P
Vest4		0.28
MutPred		0.67		Gain of methylation at R383 (P = 0.3554);.;Gain of methylation at R383 (P = 0.3554);Gain of methylation at R383 (P = 0.3554);
MVP		0.62
MPC		0.70
ClinPred		0.98	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.73

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-100275503;