1-39883466-G-T

Variant names:

• chr1-39883466-G-T
• NM_017646.6:c.26C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017646.6(TRIT1):​c.26C>A​(p.Ala9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,708 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRIT1 NM_017646.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31934428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIT1	NM_017646.6	c.26C>A	p.Ala9Glu	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.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 11	1	NM_017646.6	ENSP00000321810.5
TRIT1	ENST00000372818.5	c.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 10	1		ENSP00000361905.1
TRIT1	ENST00000462797.5	n.26C>A		non_coding_transcript_exon_variant	Exon 1 of 10	5		ENSP00000473773.1
TRIT1	ENST00000486825.6	n.8C>A		non_coding_transcript_exon_variant	Exon 1 of 8	5		ENSP00000474151.1
TRIT1	ENST00000489945.5	n.26C>A		non_coding_transcript_exon_variant	Exon 1 of 7	5		ENSP00000473745.1
TRIT1	ENST00000492612.6	n.14C>A		non_coding_transcript_exon_variant	Exon 1 of 9	5		ENSP00000473708.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444708 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 714954

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.0030	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	.;T;.
Eigen	Benign	0.036
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.26	N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.14	.;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0060	.;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	D;B;.
Vest4		0.62
MutPred		0.29		Loss of MoRF binding (P = 0.0235);Loss of MoRF binding (P = 0.0235);Loss of MoRF binding (P = 0.0235);
MVP		0.70
MPC		0.37
ClinPred		0.71	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.81

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: chr1-40349138;