rs11581557

Positions:

• chr1-39862786-A-C
• chr1-39862786-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017646.6(TRIT1):​c.175-5369T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 985,228 control chromosomes in the GnomAD database, including 2,098 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 0.090 (1239 hom., cov: 32)
  • Exomes 𝑓: 0.026 (859 hom.)
• Consequence: TRIT1 NM_017646.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIT1	NM_017646.6	c.175-5369T>G		intron_variant		ENST00000316891.10	NP_060116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIT1	ENST00000316891.10	c.175-5369T>G		intron_variant		1	NM_017646.6	ENSP00000321810	P1

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13696 AN: 152074 Hom.: 1237 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.0405

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0712

GnomAD4 exome AF: 0.0263 AC: 21897 AN: 833036 Hom.: 859 Cov.: 29 AF XY: 0.0258 AC XY: 9929 AN XY: 384686

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.0366

Gnomad4 ASJ exome AF: 0.0662

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.0284

Gnomad4 FIN exome AF: 0.0471

Gnomad4 NFE exome AF: 0.0196

Gnomad4 OTH exome AF: 0.0502

GnomAD4 genome AF: 0.0901 AC: 13716 AN: 152192 Hom.: 1239 Cov.: 32 AF XY: 0.0908 AC XY: 6758 AN XY: 74426

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.0395

Gnomad4 FIN AF: 0.0624

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0718

Alfa AF: 0.0118 Hom.: 7

Bravo AF: 0.0983

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.76
DANN	Benign	0.73

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: rs11581557; hg19: chr1-40328458;