1-100136924-A-G

Position:

• chr1-100136924-A-G

Variant summary

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

The NM_019083.3(TRMT13):​c.190A>G​(p.Lys64Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRMT13 NM_019083.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.80

Genes affected

TRMT13 (HGNC:25502): (tRNA methyltransferase 13 homolog) Predicted to enable tRNA methyltransferase activity. Predicted to be involved in tRNA methylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT13	NM_019083.3	c.190A>G	p.Lys64Glu	missense_variant	2/11	ENST00000370141.8	NP_061956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRMT13	ENST00000370141.8	c.190A>G	p.Lys64Glu	missense_variant	2/11	1	NM_019083.3	ENSP00000359160.2
TRMT13	ENST00000370139.1	c.97A>G	p.Lys33Glu	missense_variant	2/6	3		ENSP00000359158.1
TRMT13	ENST00000370143.5	c.190A>G	p.Lys64Glu	missense_variant	2/5	3		ENSP00000359162.1
TRMT13	ENST00000482437.5	n.190A>G		non_coding_transcript_exon_variant	2/8	2		ENSP00000432616.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Nov 25, 2024

The c.190A>G (p.K64E) alteration is located in exon 2 (coding exon 2) of the TRMT13 gene. This alteration results from a A to G substitution at nucleotide position 190, causing the lysine (K) at amino acid position 64 to be replaced by a glutamic acid (E). 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	0.77
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	.;T;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	3.3	.;M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.61
MutPred		0.57		Loss of methylation at K64 (P = 0.0016);Loss of methylation at K64 (P = 0.0016);.;
MVP		0.77
MPC		0.85
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.57
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-100602480;