chr11-64224717-C-A

Variant names:

• chr11-64224717-C-A
• NM_001033678.4:c.328G>T

Variant summary

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

The NM_001033678.4(TRPT1):​c.328G>T​(p.Val110Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRPT1 NM_001033678.4 missense, splice_region
• Scores: Splicing: ADA: 0.9983
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12

Genes affected

TRPT1 (HGNC:20316): (tRNA phosphotransferase 1) Predicted to enable tRNA 2'-phosphotransferase activity. Predicted to be involved in tRNA splicing, via endonucleolytic cleavage and ligation. Predicted to act upstream of or within regulation of protein kinase activity. [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 rank	MANE	Protein	UniProt
TRPT1	NM_001033678.4	c.328G>T	p.Val110Leu	missense_variant, splice_region_variant	Exon 5 of 8	ENST00000317459.11	NP_001028850.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPT1	ENST00000317459.11	c.328G>T	p.Val110Leu	missense_variant, splice_region_variant	Exon 5 of 8	1	NM_001033678.4	ENSP00000314073.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.334G>T (p.V112L) alteration is located in exon 5 (coding exon 4) of the TRPT1 gene. This alteration results from a G to T substitution at nucleotide position 334, causing the valine (V) at amino acid position 112 to be replaced by a leucine (L). 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	Uncertain	0.42
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	.;.;.;T;T;T
Eigen	Benign	-0.0087
Eigen_PC	Benign	0.079
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T;T;T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	.;M;.;M;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.3	N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.027	D;D;T;D;D;T
Sift4G	Benign	0.093	T;T;T;T;T;T
Polyphen		0.41	B;.;.;B;.;.
Vest4		0.42
MutPred		0.57		.;Gain of ubiquitination at K112 (P = 0.0773);.;Gain of ubiquitination at K112 (P = 0.0773);.;.;
MVP		0.48
MPC		0.25
ClinPred		0.82	D
GERP RS		4.3
Varity_R		0.33
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.96
SpliceAI score (max)		0.14		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: chr11-63992189;