1-39883361-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000316891.10(TRIT1):ā€‹c.131G>Cā€‹(p.Gly44Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,470 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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

TRIT1
ENST00000316891.10 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24748045).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRIT1NM_017646.6 linkuse as main transcriptc.131G>C p.Gly44Ala missense_variant 1/11 ENST00000316891.10 NP_060116.2 Q9H3H1-1Q53F11Q3T7C7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRIT1ENST00000316891.10 linkuse as main transcriptc.131G>C p.Gly44Ala missense_variant 1/111 NM_017646.6 ENSP00000321810.5 Q9H3H1-1
TRIT1ENST00000372818.5 linkuse as main transcriptc.131G>C p.Gly44Ala missense_variant 1/101 ENSP00000361905.1 Q9H3H1-4
TRIT1ENST00000462797.5 linkuse as main transcriptn.131G>C non_coding_transcript_exon_variant 1/105 ENSP00000473773.1 S4R2Z0
TRIT1ENST00000486825.6 linkuse as main transcriptn.113G>C non_coding_transcript_exon_variant 1/85 ENSP00000474151.1 S4R3C5
TRIT1ENST00000489945.5 linkuse as main transcriptn.131G>C non_coding_transcript_exon_variant 1/75 ENSP00000473745.1 B4DK89
TRIT1ENST00000492612.6 linkuse as main transcriptn.119G>C non_coding_transcript_exon_variant 1/95 ENSP00000473708.1 S4R2X1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460470
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726518
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxJun 18, 2019Not observed [at a significant frequency] in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
23
DANN
Benign
0.90
DEOGEN2
Benign
0.068
.;T;.
Eigen
Benign
-0.11
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Pathogenic
1.0
D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.48
N;N;N
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;N
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
0.42
.;N;N
REVEL
Benign
0.22
Sift
Benign
1.0
.;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.99
D;B;.
Vest4
0.40
MutPred
0.72
Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);
MVP
0.31
MPC
0.38
ClinPred
0.60
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.25
gMVP
0.88

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40349033; API