Variant 1-39883350-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017646.6(TRIT1):c.142G>A(p.Gly48Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000686 in 1,458,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

TRIT1
NM_017646.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

Variant links:

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]

TRIT1 links:

TRIT1 (HGNC:):

TRIT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3864743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIT1	NM_017646.6 linkuse as main transcript	c.142G>A	p.Gly48Ser	missense_variant	1/11	ENST00000316891.10	NP_060116.2	Q9H3H1-1Q53F11Q3T7C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIT1	ENST00000316891.10 linkuse as main transcript	c.142G>A	p.Gly48Ser	missense_variant	1/11	1	NM_017646.6	ENSP00000321810.5	Q9H3H1-1
TRIT1	ENST00000372818.5 linkuse as main transcript	c.142G>A	p.Gly48Ser	missense_variant	1/10	1		ENSP00000361905.1	Q9H3H1-4
TRIT1	ENST00000462797.5 linkuse as main transcript	n.142G>A		non_coding_transcript_exon_variant	1/10	5		ENSP00000473773.1	S4R2Z0
TRIT1	ENST00000486825.6 linkuse as main transcript	n.124G>A		non_coding_transcript_exon_variant	1/8	5		ENSP00000474151.1	S4R3C5
TRIT1	ENST00000489945.5 linkuse as main transcript	n.142G>A		non_coding_transcript_exon_variant	1/7	5		ENSP00000473745.1	B4DK89
TRIT1	ENST00000492612.6 linkuse as main transcript	n.130G>A		non_coding_transcript_exon_variant	1/9	5		ENSP00000473708.1	S4R2X1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241354

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131556

show subpopulations

Gnomad AFR exome

AF:

0.0000658

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1458724

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725560

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2024

The c.142G>A (p.G48S) alteration is located in exon 1 (coding exon 1) of the TRIT1 gene. This alteration results from a G to A substitution at nucleotide position 142, causing the glycine (G) at amino acid position 48 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

.;T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.0

L;L;L

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.8

.;N;N

REVEL

Benign

0.14

Sift

Benign

0.079

.;T;T

Sift4G

Benign

0.073

T;T;T

Polyphen

1.0

D;P;.

Vest4

0.47

MutPred

0.42

Gain of phosphorylation at G48 (P = 0.0489);Gain of phosphorylation at G48 (P = 0.0489);Gain of phosphorylation at G48 (P = 0.0489);

MVP

0.81

MPC

0.29

ClinPred

0.78

GERP RS

5.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.14

gMVP

0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over