chr11-64224329-T-A

Variant names:

• chr11-64224329-T-A
• rs1059440
• NM_001033678.4:c.515A>T

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.515A>T​(p.His172Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRPT1 NM_001033678.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 59 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=0.23125929).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPT1	NM_001033678.4	MANE Select	c.515A>T	p.His172Leu	missense	Exon 6 of 8	NP_001028850.2
	TRPT1	NM_001160389.2		c.521A>T	p.His174Leu	missense	Exon 6 of 8	NP_001153861.1
	TRPT1	NM_001160393.1		c.515A>T	p.His172Leu	missense	Exon 5 of 7	NP_001153865.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPT1	ENST00000317459.11	TSL:1 MANE Select	c.515A>T	p.His172Leu	missense	Exon 6 of 8	ENSP00000314073.6
	TRPT1	ENST00000394547.7	TSL:1	c.368A>T	p.His123Leu	missense	Exon 5 of 7	ENSP00000378051.3
	TRPT1	ENST00000394546.6	TSL:5	c.521A>T	p.His174Leu	missense	Exon 6 of 8	ENSP00000378050.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461412 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726970

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 7022

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.095
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.055	T
Polyphen		0.024	B
Vest4		0.24
MutPred		0.47		Loss of sheet (P = 0.0181)
MVP		0.23
MPC		0.27
ClinPred		0.77	D
GERP RS		2.6
PromoterAI		-0.038	Neutral
Varity_R		0.22
gMVP		0.61
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1059440; hg19: chr11-63991801;