1-39858538-T-G

Variant names:

• chr1-39858538-T-G
• rs17570439
• NM_017646.6:c.175-1121A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017646.6(TRIT1):​c.175-1121A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TRIT1 NM_017646.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 6 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]

TRIT1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• combined oxidative phosphorylation deficiency 35

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIT1	NM_017646.6	MANE Select	c.175-1121A>C		intron	N/A	NP_060116.2
	TRIT1	NM_001312691.1		c.175-1121A>C		intron	N/A	NP_001299620.1
	TRIT1	NM_001312692.1		c.175-5662A>C		intron	N/A	NP_001299621.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIT1	ENST00000316891.10	TSL:1 MANE Select	c.175-1121A>C		intron	N/A	ENSP00000321810.5
	TRIT1	ENST00000372818.5	TSL:1	c.175-1121A>C		intron	N/A	ENSP00000361905.1
	TRIT1	ENST00000441669.6	TSL:1	c.175-5662A>C		intron	N/A	ENSP00000388333.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 13600

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.73
DANN	Benign	0.12
PhyloP100		0.15

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: rs17570439; hg19: chr1-40324210;