1-39883356-G-T

Variant names:

• chr1-39883356-G-T
• rs747839263
• NM_017646.6:c.136C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_017646.6(TRIT1):​c.136C>A​(p.Arg46Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,958 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIT1 NM_017646.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 0 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=1.44 with no splicing effect.

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.136C>A	p.Arg46Arg	synonymous	Exon 1 of 11	NP_060116.2
	TRIT1	NM_001312691.1		c.136C>A	p.Arg46Arg	synonymous	Exon 1 of 10	NP_001299620.1	Q9H3H1-4
	TRIT1	NM_001312692.1		c.136C>A	p.Arg46Arg	synonymous	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.136C>A	p.Arg46Arg	synonymous	Exon 1 of 11	ENSP00000321810.5	Q9H3H1-1
	TRIT1	ENST00000372818.5	TSL:1	c.136C>A	p.Arg46Arg	synonymous	Exon 1 of 10	ENSP00000361905.1	Q9H3H1-4
	TRIT1	ENST00000441669.6	TSL:1	c.136C>A	p.Arg46Arg	synonymous	Exon 1 of 9	ENSP00000388333.2	Q9H3H1-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244504 AF XY: 0.00000752

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: 0.00000913

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459958 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726202

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5502

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111382

Other (OTH) AF: 0.00 AC: 0 AN: 60238

GnomAD4 genome Cov.: 32

Alfa AF: 0.000111 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		1.4
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=300/0	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: rs747839263; hg19: chr1-40349028;