chr1-39858538-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017646.6(TRIT1):​c.175-1121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,140 control chromosomes in the GnomAD database, including 2,715 homozygotes. 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: 𝑓 0.18 (2715 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIT1	NM_017646.6	MANE Select	c.175-1121A>G		intron	N/A	NP_060116.2
	TRIT1	NM_001312691.1		c.175-1121A>G		intron	N/A	NP_001299620.1
	TRIT1	NM_001312692.1		c.175-5662A>G		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>G		intron	N/A	ENSP00000321810.5
	TRIT1	ENST00000372818.5	TSL:1	c.175-1121A>G		intron	N/A	ENSP00000361905.1
	TRIT1	ENST00000441669.6	TSL:1	c.175-5662A>G		intron	N/A	ENSP00000388333.2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27910 AN: 152022 Hom.: 2714 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00960

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.183 AC: 27908 AN: 152140 Hom.: 2715 Cov.: 32 AF XY: 0.178 AC XY: 13219 AN XY: 74386

African (AFR) AF: 0.177 AC: 7339 AN: 41486

American (AMR) AF: 0.140 AC: 2137 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3472

East Asian (EAS) AF: 0.00962 AC: 50 AN: 5196

South Asian (SAS) AF: 0.201 AC: 966 AN: 4812

European-Finnish (FIN) AF: 0.143 AC: 1515 AN: 10586

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14770 AN: 67986

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.202 Hom.: 13600

Bravo AF: 0.179

Asia WGS AF: 0.111 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.16
PhyloP100		0.15
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: rs17570439; hg19: chr1-40324210;