chr11-64224853-C-T

Variant names:

• chr11-64224853-C-T
• rs1946880018
• NM_001033678.4:c.275G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033678.4(TRPT1):​c.275G>A​(p.Gly92Glu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRPT1 NM_001033678.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12149358).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033678.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPT1	NM_001033678.4	MANE Select	c.275G>A	p.Gly92Glu	missense	Exon 4 of 8	NP_001028850.2	Q86TN4-1
	TRPT1	NM_001160389.2		c.275G>A	p.Gly92Glu	missense	Exon 4 of 8	NP_001153861.1	Q86TN4-4
	TRPT1	NM_001160393.1		c.275G>A	p.Gly92Glu	missense	Exon 3 of 7	NP_001153865.1	Q86TN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPT1	ENST00000317459.11	TSL:1 MANE Select	c.275G>A	p.Gly92Glu	missense	Exon 4 of 8	ENSP00000314073.6	Q86TN4-1
	TRPT1	ENST00000394547.7	TSL:1	c.128G>A	p.Gly43Glu	missense	Exon 3 of 7	ENSP00000378051.3	Q86TN4-2
	TRPT1	ENST00000394546.6	TSL:5	c.275G>A	p.Gly92Glu	missense	Exon 4 of 8	ENSP00000378050.2	Q86TN4-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.72
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.085
Sift	Benign	0.69	T
Sift4G	Benign	0.84	T
Polyphen		0.96	D
Vest4		0.49
MutPred		0.41		Gain of solvent accessibility (P = 0.024)
MVP		0.31
MPC		0.37
ClinPred		0.14	T
GERP RS		3.8
PromoterAI		0.0052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.099
gMVP		0.49
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1946880018; hg19: chr11-63992325;