1-39883478-G-C

Variant names:

• chr1-39883478-G-C
• rs766933115
• NM_017646.6:c.14C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017646.6(TRIT1):​c.14C>G​(p.Ala5Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,443,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000014 (0 hom.)
• Consequence: TRIT1 NM_017646.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21

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

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=0.22038627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIT1	NM_017646.6	c.14C>G	p.Ala5Gly	missense_variant	Exon 1 of 11	ENST00000316891.10	NP_060116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIT1	ENST00000316891.10	c.14C>G	p.Ala5Gly	missense_variant	Exon 1 of 11	1	NM_017646.6	ENSP00000321810.5
TRIT1	ENST00000372818.5	c.14C>G	p.Ala5Gly	missense_variant	Exon 1 of 10	1		ENSP00000361905.1
TRIT1	ENST00000462797.5	n.14C>G		non_coding_transcript_exon_variant	Exon 1 of 10	5		ENSP00000473773.1
TRIT1	ENST00000489945.5	n.14C>G		non_coding_transcript_exon_variant	Exon 1 of 7	5		ENSP00000473745.1
TRIT1	ENST00000492612.6	n.2C>G		non_coding_transcript_exon_variant	Exon 1 of 9	5		ENSP00000473708.1
TRIT1	ENST00000486825.6	n.-5C>G		upstream_gene_variant		5		ENSP00000474151.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1443066 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 713772

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14C>G (p.A5G) alteration is located in exon 1 (coding exon 1) of the TRIT1 gene. This alteration results from a C to G substitution at nucleotide position 14, causing the alanine (A) at amino acid position 5 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.015	.;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.0041
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.21	.;N;N
REVEL	Benign	0.13
Sift	Benign	0.21	.;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.66	P;P;.
Vest4		0.51
MutPred		0.14		Gain of disorder (P = 0.12);Gain of disorder (P = 0.12);Gain of disorder (P = 0.12);
MVP		0.63
MPC		0.28
ClinPred		0.70	D
GERP RS		4.8
Varity_R		0.053
gMVP		0.48

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

Other links and lift over

dbSNP: rs766933115; hg19: chr1-40349150;