Genetic Variant TRIT1:p.Arg8Gln (chr1-39883469-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_017646.6(TRIT1):c.23G>A(p.Arg8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,595,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TRIT1
NM_017646.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.983

Publications

3 publications found

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:40386): (MYCL antisense RNA 1)

MYCL-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27225792).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIT1	NM_017646.6	MANE Select	c.23G>A	p.Arg8Gln	missense	Exon 1 of 11	NP_060116.2
TRIT1	NM_001312691.1		c.23G>A	p.Arg8Gln	missense	Exon 1 of 10	NP_001299620.1	Q9H3H1-4
TRIT1	NM_001312692.1		c.23G>A	p.Arg8Gln	missense	Exon 1 of 9	NP_001299621.1	Q9H3H1-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIT1	ENST00000316891.10	TSL:1 MANE Select	c.23G>A	p.Arg8Gln	missense	Exon 1 of 11	ENSP00000321810.5	Q9H3H1-1
TRIT1	ENST00000372818.5	TSL:1	c.23G>A	p.Arg8Gln	missense	Exon 1 of 10	ENSP00000361905.1	Q9H3H1-4
TRIT1	ENST00000441669.6	TSL:1	c.23G>A	p.Arg8Gln	missense	Exon 1 of 9	ENSP00000388333.2	Q9H3H1-5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

AC:

AN:

242292

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1443660

Hom.:

Cov.:

AF XY:

0.00000420

AC XY:

AN XY:

714262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33082

American (AMR)

AF:

0.00

AC:

AN:

44246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.00

AC:

AN:

39046

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5496

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1098012

Other (OTH)

AF:

0.00

AC:

AN:

59316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

Eigen

Benign

0.14

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.038

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

PhyloP100

0.98

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.080

REVEL

Benign

0.13

Sift

Uncertain

0.012

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.50

MutPred

0.37

Loss of MoRF binding (P = 0.0131)

MVP

0.66

MPC

0.91

ClinPred

0.94

GERP RS

4.8

PromoterAI

-0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.57

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over