rs230310

Variant names:

• chr1-39842047-A-G
• rs230310
• NM_017646.6:c.1235-134T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-39842047-A-G
• chr1-39842047-A-T

Variant summary

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

The NM_017646.6(TRIT1):​c.1235-134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 957,182 control chromosomes in the GnomAD database, including 288,736 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 0.81 (50608 hom., cov: 33)
  • Exomes 𝑓: 0.77 (238128 hom.)
• Consequence: TRIT1 NM_017646.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIT1	NM_017646.6	c.1235-134T>C		intron_variant	Intron 10 of 10	ENST00000316891.10	NP_060116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIT1	ENST00000316891.10	c.1235-134T>C		intron_variant	Intron 10 of 10	1	NM_017646.6	ENSP00000321810.5
TRIT1	ENST00000372818.5	c.1157-134T>C		intron_variant	Intron 9 of 9	1		ENSP00000361905.1
TRIT1	ENST00000462797.5	n.*75-134T>C		intron_variant	Intron 9 of 9	5		ENSP00000473773.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123213 AN: 152122 Hom.: 50558 Cov.: 33

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.782

GnomAD4 exome AF: 0.767 AC: 617572 AN: 804940 Hom.: 238128 AF XY: 0.767 AC XY: 312641 AN XY: 407506

African (AFR) AF: 0.951 AC: 17442 AN: 18344

American (AMR) AF: 0.664 AC: 12161 AN: 18318

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 13955 AN: 15830

East Asian (EAS) AF: 0.710 AC: 22844 AN: 32184

South Asian (SAS) AF: 0.755 AC: 38926 AN: 51538

European-Finnish (FIN) AF: 0.788 AC: 26093 AN: 33100

Middle Eastern (MID) AF: 0.808 AC: 2819 AN: 3490

European-Non Finnish (NFE) AF: 0.764 AC: 454243 AN: 594678

Other (OTH) AF: 0.777 AC: 29089 AN: 37458

GnomAD4 genome AF: 0.810 AC: 123318 AN: 152242 Hom.: 50608 Cov.: 33 AF XY: 0.807 AC XY: 60067 AN XY: 74420

African (AFR) AF: 0.947 AC: 39364 AN: 41572

American (AMR) AF: 0.693 AC: 10601 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3090 AN: 3472

East Asian (EAS) AF: 0.679 AC: 3514 AN: 5176

South Asian (SAS) AF: 0.758 AC: 3660 AN: 4826

European-Finnish (FIN) AF: 0.782 AC: 8272 AN: 10576

Middle Eastern (MID) AF: 0.777 AC: 227 AN: 292

European-Non Finnish (NFE) AF: 0.768 AC: 52222 AN: 68004

Other (OTH) AF: 0.777 AC: 1642 AN: 2112

Alfa AF: 0.776 Hom.: 86333

Bravo AF: 0.809

Asia WGS AF: 0.757 AC: 2633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.76
PhyloP100		0.29
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: rs230310; hg19: chr1-40307719;