chr11-64224329-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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: 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
• 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: Benign. The variant received -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.

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.515A>G	p.His172Arg	missense	Exon 6 of 8	NP_001028850.2	Q86TN4-1
	TRPT1	NM_001160389.2		c.521A>G	p.His174Arg	missense	Exon 6 of 8	NP_001153861.1	Q86TN4-4
	TRPT1	NM_001160393.1		c.515A>G	p.His172Arg	missense	Exon 5 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.515A>G	p.His172Arg	missense	Exon 6 of 8	ENSP00000314073.6	Q86TN4-1
	TRPT1	ENST00000394547.7	TSL:1	c.368A>G	p.His123Arg	missense	Exon 5 of 7	ENSP00000378051.3	Q86TN4-2
	TRPT1	ENST00000394546.6	TSL:5	c.521A>G	p.His174Arg	missense	Exon 6 of 8	ENSP00000378050.2	Q86TN4-4

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

GnomAD2 exomes AF: 0.178 AC: 44634 AN: 250610 AF XY: 0.173

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 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

African (AFR) AF: 0.100 AC: 3354 AN: 33478

American (AMR) AF: 0.308 AC: 13786 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 4663 AN: 26136

East Asian (EAS) AF: 0.184 AC: 7318 AN: 39684

South Asian (SAS) AF: 0.0968 AC: 8346 AN: 86258

European-Finnish (FIN) AF: 0.170 AC: 8992 AN: 52970

Middle Eastern (MID) AF: 0.190 AC: 1094 AN: 5768

European-Non Finnish (NFE) AF: 0.172 AC: 191229 AN: 1111952

Other (OTH) AF: 0.180 AC: 10870 AN: 60382

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

African (AFR) AF: 0.105 AC: 4352 AN: 41546

American (AMR) AF: 0.281 AC: 4298 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3472

East Asian (EAS) AF: 0.188 AC: 976 AN: 5178

South Asian (SAS) AF: 0.0889 AC: 429 AN: 4826

European-Finnish (FIN) AF: 0.175 AC: 1850 AN: 10594

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11790 AN: 67998

Other (OTH) AF: 0.200 AC: 423 AN: 2110

Alfa AF: 0.170 Hom.: 7022

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 v4.9

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
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.078
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.12	T
Polyphen		0.10	B
Vest4		0.099
MPC		0.27
ClinPred		0.020	T
GERP RS		2.6
PromoterAI		-0.019	Neutral
Varity_R		0.15
gMVP		0.55
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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