NM_017646.6:c.33C>T

Variant names:

• chr1-39883459-G-A
• rs3845570
• NM_017646.6:c.33C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017646.6(TRIT1):​c.33C>T​(p.Pro11Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,603,634 control chromosomes in the GnomAD database, including 144,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P11P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.46 (16390 hom., cov: 32)
  • Exomes 𝑓: 0.42 (128274 hom.)
• Consequence: TRIT1 NM_017646.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.156
• Publications: 19 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-39883459-G-A is Benign according to our data. Variant chr1-39883459-G-A is described in ClinVar as Benign. ClinVar VariationId is 1342274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.156 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

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.33C>T	p.Pro11Pro	synonymous	Exon 1 of 11	NP_060116.2
	TRIT1	NM_001312691.1		c.33C>T	p.Pro11Pro	synonymous	Exon 1 of 10	NP_001299620.1	Q9H3H1-4
	TRIT1	NM_001312692.1		c.33C>T	p.Pro11Pro	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.33C>T	p.Pro11Pro	synonymous	Exon 1 of 11	ENSP00000321810.5	Q9H3H1-1
	TRIT1	ENST00000372818.5	TSL:1	c.33C>T	p.Pro11Pro	synonymous	Exon 1 of 10	ENSP00000361905.1	Q9H3H1-4
	TRIT1	ENST00000441669.6	TSL:1	c.33C>T	p.Pro11Pro	synonymous	Exon 1 of 9	ENSP00000388333.2	Q9H3H1-5

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69412 AN: 151940 Hom.: 16359 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.414

GnomAD2 exomes AF: 0.442 AC: 108640 AN: 246060 AF XY: 0.434

Gnomad AFR exome AF: 0.582

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.595

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.392

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.418 AC: 606042 AN: 1451576 Hom.: 128274 Cov.: 45 AF XY: 0.417 AC XY: 300368 AN XY: 719920

African (AFR) AF: 0.583 AC: 19414 AN: 33300

American (AMR) AF: 0.461 AC: 20511 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 12350 AN: 26062

East Asian (EAS) AF: 0.603 AC: 23748 AN: 39358

South Asian (SAS) AF: 0.444 AC: 38184 AN: 86040

European-Finnish (FIN) AF: 0.408 AC: 21651 AN: 53044

Middle Eastern (MID) AF: 0.354 AC: 1986 AN: 5604

European-Non Finnish (NFE) AF: 0.401 AC: 442403 AN: 1103940

Other (OTH) AF: 0.432 AC: 25795 AN: 59772

GnomAD4 genome AF: 0.457 AC: 69491 AN: 152058 Hom.: 16390 Cov.: 32 AF XY: 0.456 AC XY: 33903 AN XY: 74334

African (AFR) AF: 0.576 AC: 23882 AN: 41464

American (AMR) AF: 0.433 AC: 6615 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3072 AN: 5154

South Asian (SAS) AF: 0.455 AC: 2192 AN: 4822

European-Finnish (FIN) AF: 0.398 AC: 4210 AN: 10586

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26732 AN: 67980

Other (OTH) AF: 0.414 AC: 872 AN: 2108

Alfa AF: 0.427 Hom.: 13715

Bravo AF: 0.465

Asia WGS AF: 0.555 AC: 1930 AN: 3478

EpiCase AF: 0.390

EpiControl AF: 0.384

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Combined oxidative phosphorylation deficiency 35 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.6
DANN	Benign	0.83
PhyloP100		-0.16
PromoterAI		0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs3845570; hg19: chr1-40349131; COSMIC: COSV57547751; COSMIC: COSV57547751;