chr1-39883476-C-T

Variant names:

• chr1-39883476-C-T
• rs138415849
• NM_017646.6:c.16G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017646.6(TRIT1):​c.16G>A​(p.Ala6Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000846 in 1,596,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (0 hom.)
• Consequence: TRIT1 NM_017646.6 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 4.02
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042782456).

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.16G>A	p.Ala6Thr	missense	Exon 1 of 11	NP_060116.2
	TRIT1	NM_001312691.1		c.16G>A	p.Ala6Thr	missense	Exon 1 of 10	NP_001299620.1	Q9H3H1-4
	TRIT1	NM_001312692.1		c.16G>A	p.Ala6Thr	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.16G>A	p.Ala6Thr	missense	Exon 1 of 11	ENSP00000321810.5	Q9H3H1-1
	TRIT1	ENST00000372818.5	TSL:1	c.16G>A	p.Ala6Thr	missense	Exon 1 of 10	ENSP00000361905.1	Q9H3H1-4
	TRIT1	ENST00000441669.6	TSL:1	c.16G>A	p.Ala6Thr	missense	Exon 1 of 9	ENSP00000388333.2	Q9H3H1-5

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000429 AC: 105 AN: 244576 AF XY: 0.000443

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.000587

Gnomad ASJ exome AF: 0.000203

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000703

Gnomad OTH exome AF: 0.000671

GnomAD4 exome AF: 0.000887 AC: 1280 AN: 1443758 Hom.: 0 Cov.: 32 AF XY: 0.000851 AC XY: 608 AN XY: 714178

African (AFR) AF: 0.0000907 AC: 3 AN: 33068

American (AMR) AF: 0.000588 AC: 26 AN: 44202

Ashkenazi Jewish (ASJ) AF: 0.000154 AC: 4 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39036

South Asian (SAS) AF: 0.00 AC: 0 AN: 85806

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 0.00110 AC: 1207 AN: 1097844

Other (OTH) AF: 0.000640 AC: 38 AN: 59392

GnomAD4 genome AF: 0.000459 AC: 70 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74500

African (AFR) AF: 0.0000722 AC: 3 AN: 41576

American (AMR) AF: 0.000980 AC: 15 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000699 Hom.: 0

Bravo AF: 0.000597

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000931 AC: 8

ExAC AF: 0.000429 AC: 52

EpiCase AF: 0.000873

EpiControl AF: 0.000653

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Combined oxidative phosphorylation deficiency 35 (1)
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.0086
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.089
Sift	Benign	0.055	T
Sift4G	Benign	0.43	T
Polyphen		0.029	B
Vest4		0.53
MVP		0.65
MPC		0.37
ClinPred		0.11	T
GERP RS		4.8
PromoterAI		-0.30	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.080
gMVP		0.50
Mutation Taster		=88/12	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: rs138415849; hg19: chr1-40349148;