11-64224555-C-T

Variant names:

• chr11-64224555-C-T
• rs757156680
• NM_001033678.4:c.490G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001033678.4(TRPT1):​c.490G>A​(p.Gly164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,567,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: TRPT1 NM_001033678.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.875
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101742566).
• BP6: Variant 11-64224555-C-T is Benign according to our data. Variant chr11-64224555-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3462281.Status of the report is criteria_provided_single_submitter, 1 stars.

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.490G>A	p.Gly164Ser	missense	Exon 5 of 8	NP_001028850.2	Q86TN4-1
	TRPT1	NM_001160389.2		c.496G>A	p.Gly166Ser	missense	Exon 5 of 8	NP_001153861.1	Q86TN4-4
	TRPT1	NM_001160393.1		c.490G>A	p.Gly164Ser	missense	Exon 4 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.490G>A	p.Gly164Ser	missense	Exon 5 of 8	ENSP00000314073.6	Q86TN4-1
	TRPT1	ENST00000394547.7	TSL:1	c.343G>A	p.Gly115Ser	missense	Exon 4 of 7	ENSP00000378051.3	Q86TN4-2
	TRPT1	ENST00000394546.6	TSL:5	c.496G>A	p.Gly166Ser	missense	Exon 5 of 8	ENSP00000378050.2	Q86TN4-4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000140 AC: 3 AN: 213904 AF XY: 0.0000176

Gnomad AFR exome AF: 0.0000629

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000989 AC: 14 AN: 1415702 Hom.: 0 Cov.: 32 AF XY: 0.0000115 AC XY: 8 AN XY: 698508

African (AFR) AF: 0.0000307 AC: 1 AN: 32608

American (AMR) AF: 0.00 AC: 0 AN: 40616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22608

East Asian (EAS) AF: 0.000178 AC: 7 AN: 39278

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5524

European-Non Finnish (NFE) AF: 0.00000460 AC: 5 AN: 1086920

Other (OTH) AF: 0.00 AC: 0 AN: 58446

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.076
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.88
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.056
Sift	Benign	0.078	T
Sift4G	Benign	0.14	T
Polyphen		0.012	B
Vest4		0.15
MVP		0.32
MPC		0.22
ClinPred		0.052	T
GERP RS		2.6
PromoterAI		0.0034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.71
Mutation Taster		=90/10	polymorphism

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: rs757156680; hg19: chr11-63992027; COSMIC: COSV54172590; COSMIC: COSV54172590;