NM_017646.6:c.136C>T

Variant names:

• chr1-39883356-G-A
• rs747839263
• NM_017646.6:c.136C>T

Variant summary

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

The NM_017646.6(TRIT1):​c.136C>T​(p.Arg46Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000493 in 1,459,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: TRIT1 NM_017646.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

Genes affected

TRIT1 (HGNC:20286): (tRNA isopentenyltransferase 1) This gene encodes a protein that that is targeted to the mitochondrion and modifies transfer RNAs (tRNAs) by adding a dimethylallyl group onto the adenine at position 37. This modification is important for maintaining the correct reading frame during protein translation. This gene is considered a tumor suppressor and its expression can decrease cell growth. Alternative splicing results in multiple transcripts variants, most of which are likely non-functional. [provided by RefSeq, Aug 2015]

MYCL-AS1 (HGNC:40386): (MYCL antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017646.6. 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
	TRIT1	NM_017646.6	MANE Select	c.136C>T	p.Arg46Trp	missense	Exon 1 of 11	NP_060116.2
	TRIT1	NM_001312691.1		c.136C>T	p.Arg46Trp	missense	Exon 1 of 10	NP_001299620.1	Q9H3H1-4
	TRIT1	NM_001312692.1		c.136C>T	p.Arg46Trp	missense	Exon 1 of 9	NP_001299621.1	Q9H3H1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIT1	ENST00000316891.10	TSL:1 MANE Select	c.136C>T	p.Arg46Trp	missense	Exon 1 of 11	ENSP00000321810.5	Q9H3H1-1
	TRIT1	ENST00000372818.5	TSL:1	c.136C>T	p.Arg46Trp	missense	Exon 1 of 10	ENSP00000361905.1	Q9H3H1-4
	TRIT1	ENST00000441669.6	TSL:1	c.136C>T	p.Arg46Trp	missense	Exon 1 of 9	ENSP00000388333.2	Q9H3H1-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 244504 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000493 AC: 72 AN: 1459958 Hom.: 0 Cov.: 30 AF XY: 0.0000386 AC XY: 28 AN XY: 726202

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5502

European-Non Finnish (NFE) AF: 0.0000630 AC: 70 AN: 1111382

Other (OTH) AF: 0.0000332 AC: 2 AN: 60238

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.74	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.56		Loss of disorder (P = 0.0689)
MVP		0.68
MPC		0.71
ClinPred		0.99	D
GERP RS		2.5
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.82
Mutation Taster		=62/38	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: rs747839263; hg19: chr1-40349028;