1-39883439-C-T

Variant names:

• chr1-39883439-C-T
• rs146989823
• NM_017646.6:c.53G>A

Variant summary

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

The NM_017646.6(TRIT1):​c.53G>A​(p.Gly18Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. G18V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIT1 NM_017646.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.709

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=0.08707744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIT1	NM_017646.6	c.53G>A	p.Gly18Asp	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.53G>A	p.Gly18Asp	missense_variant	Exon 1 of 11	1	NM_017646.6	ENSP00000321810.5
TRIT1	ENST00000372818.5	c.53G>A	p.Gly18Asp	missense_variant	Exon 1 of 10	1		ENSP00000361905.1
TRIT1	ENST00000462797.5	n.53G>A		non_coding_transcript_exon_variant	Exon 1 of 10	5		ENSP00000473773.1
TRIT1	ENST00000486825.6	n.35G>A		non_coding_transcript_exon_variant	Exon 1 of 8	5		ENSP00000474151.1
TRIT1	ENST00000489945.5	n.53G>A		non_coding_transcript_exon_variant	Exon 1 of 7	5		ENSP00000473745.1
TRIT1	ENST00000492612.6	n.41G>A		non_coding_transcript_exon_variant	Exon 1 of 9	5		ENSP00000473708.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458618 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724942

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.82
DEOGEN2	Benign	0.021	.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.030	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.57	.;N;N
REVEL	Benign	0.0090
Sift	Benign	0.14	.;T;T
Sift4G	Benign	0.63	T;T;T
Polyphen		0.74	P;B;.
Vest4		0.32
MutPred		0.40		Loss of MoRF binding (P = 0.0376);Loss of MoRF binding (P = 0.0376);Loss of MoRF binding (P = 0.0376);
MVP		0.31
MPC		0.36
ClinPred		0.069	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.57

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: rs146989823; hg19: chr1-40349111;