11-64224329-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033678.4(TRPT1):c.515A>G(p.His172Arg) variant causes a missense change. The variant allele was found at a frequency of 0.17 in 1,613,572 control chromosomes in the GnomAD database, including 24,734 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2307 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22427 hom.)
• Consequence: TRPT1 NM_001033678.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058959126).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPT1	NM_001033678.4	c.515A>G	p.His172Arg	missense_variant	6/8	ENST00000317459.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPT1	ENST00000317459.11	c.515A>G	p.His172Arg	missense_variant	6/8	1	NM_001033678.4	P4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24887 AN: 152112 Hom.: 2303 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.178 AC: 44634 AN: 250610 Hom.: 4530 AF XY: 0.173 AC XY: 23502 AN XY: 135516

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.187

Gnomad SAS exome AF: 0.0984

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.171 AC: 249652 AN: 1461342 Hom.: 22427 Cov.: 34 AF XY: 0.169 AC XY: 122684 AN XY: 726942

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.0968

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.164 AC: 24903 AN: 152230 Hom.: 2307 Cov.: 33 AF XY: 0.166 AC XY: 12344 AN XY: 74434

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.0889

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.200

Alfa AF: 0.171 Hom.: 4670

Bravo AF: 0.171

TwinsUK AF: 0.173 AC: 640

ALSPAC AF: 0.167 AC: 644

ESP6500AA AF: 0.105 AC: 464

ESP6500EA AF: 0.173 AC: 1483

ExAC AF: 0.169 AC: 20564

Asia WGS AF: 0.152 AC: 527 AN: 3478

EpiCase AF: 0.174

EpiControl AF: 0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	18
Dann	Benign	0.90
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;T;T
MetaRNN	Benign	0.0059	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.96	N;N;N;N;N;N;N
REVEL	Benign	0.078
Sift	Uncertain	0.0090	D;D;D;T;D;D;T
Sift4G	Benign	0.12	T;T;T;D;T;T;T
Polyphen		0.10	B;.;.;.;B;.;.
Vest4		0.099
MPC		0.27
ClinPred		0.020	T
GERP RS		2.6
Varity_R		0.15
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1059440; hg19: chr11-63991801; COSMIC: COSV54172991; COSMIC: COSV54172991;