chr1-39842047-A-G

Position:

• chr1-39842047-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TRIT1	NM_017646.6	c.1235-134T>C		intron_variant		ENST00000316891.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIT1	ENST00000316891.10	c.1235-134T>C		intron_variant		1	NM_017646.6	P1

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

Gnomad4 AFR exome AF: 0.951

Gnomad4 AMR exome AF: 0.664

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 0.710

Gnomad4 SAS exome AF: 0.755

Gnomad4 FIN exome AF: 0.788

Gnomad4 NFE exome AF: 0.764

Gnomad4 OTH exome AF: 0.777

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

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.890

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.777

Alfa AF: 0.771 Hom.: 61582

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs230310; hg19: chr1-40307719;