X-101020514-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

1
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46
Variant links:
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]

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ACMG classification

Classification made for transcript

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
TRMT2BNM_024917.6 linkc.1141G>A p.Asp381Asn missense_variant Exon 11 of 14 ENST00000372936.4 NP_079193.2 Q96GJ1-1A0A024RCF5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRMT2BENST00000372936.4 linkc.1141G>A p.Asp381Asn missense_variant Exon 11 of 14 1 NM_024917.6 ENSP00000362027.3 Q96GJ1-1
TRMT2BENST00000372935.5 linkc.1141G>A p.Asp381Asn missense_variant Exon 11 of 14 1 ENSP00000362026.1 Q96GJ1-1
TRMT2BENST00000545398.5 linkc.1141G>A p.Asp381Asn missense_variant Exon 10 of 13 1 ENSP00000438134.1 Q96GJ1-1
TRMT2BENST00000372939.5 linkc.1006G>A p.Asp336Asn missense_variant Exon 11 of 14 1 ENSP00000362030.1 Q96GJ1-3

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
LINK: link

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; API