chr1-39883439-C-A

Position:

chr1-39883439-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017646.6(TRIT1):c.53G>T(p.Gly18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000415 in 1,610,932 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 3 hom. )

Consequence

TRIT1
NM_017646.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.709

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:

MYCL-AS1 (HGNC:):

MYCL-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004780054).

BP6

Variant 1-39883439-C-A is Benign according to our data. Variant chr1-39883439-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1195476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000289 (44/152318) while in subpopulation SAS AF= 0.00828 (40/4830). AF 95% confidence interval is 0.00625. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIT1	NM_017646.6 linkuse as main transcript	c.53G>T	p.Gly18Val	missense_variant	1/11	ENST00000316891.10
MYCL-AS1	NR_183424.1 linkuse as main transcript	n.272+18C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIT1	ENST00000316891.10 linkuse as main transcript	c.53G>T	p.Gly18Val	missense_variant	1/11	1	NM_017646.6	P1	Q9H3H1-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000861

AC:

214

AN:

248678

Hom.:

AF XY:

0.00113

AC XY:

152

AN XY:

135004

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00677

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000428

AC:

624

AN:

1458614

Hom.:

Cov.:

AF XY:

0.000610

AC XY:

442

AN XY:

724938

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00672

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000721

Gnomad4 OTH exome

AF:

0.000548

GnomAD4 genome

AF:

0.000289

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000549

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.00108

AC:

131

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 07, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 15, 2023	- -

TRIT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 19, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.0

DANN

Benign

0.67

DEOGEN2

Benign

0.013

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.72

T;T;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;L

MutationTaster

Benign

1.0

D;D;D;D;N

PrimateAI

Benign

0.46

PROVEAN

Benign

0.21

.;N;N

REVEL

Benign

0.014

Sift

Benign

0.26

.;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.32

MutPred

0.44

Loss of disorder (P = 0.064);Loss of disorder (P = 0.064);Loss of disorder (P = 0.064);

MVP

0.40

MPC

0.38

ClinPred

0.0074

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

gMVP

0.60

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

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