rs11581557

Variant names:

• chr1-39862786-A-C
• rs11581557
• NM_017646.6:c.175-5369T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-39862786-A-C
• chr1-39862786-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.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
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 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.175-5369T>G		intron	N/A	NP_060116.2
	TRIT1	NM_001312691.1		c.175-5369T>G		intron	N/A	NP_001299620.1
	TRIT1	NM_001312692.1		c.175-9910T>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.175-5369T>G		intron	N/A	ENSP00000321810.5
	TRIT1	ENST00000372818.5	TSL:1	c.175-5369T>G		intron	N/A	ENSP00000361905.1
	TRIT1	ENST00000441669.6	TSL:1	c.175-9910T>G		intron	N/A	ENSP00000388333.2

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

African (AFR) AF: 0.228 AC: 3604 AN: 15780

American (AMR) AF: 0.0366 AC: 36 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 341 AN: 5152

East Asian (EAS) AF: 0.302 AC: 1094 AN: 3626

South Asian (SAS) AF: 0.0284 AC: 467 AN: 16458

European-Finnish (FIN) AF: 0.0471 AC: 13 AN: 276

Middle Eastern (MID) AF: 0.0321 AC: 52 AN: 1620

European-Non Finnish (NFE) AF: 0.0196 AC: 14921 AN: 761844

Other (OTH) AF: 0.0502 AC: 1369 AN: 27296

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

African (AFR) AF: 0.212 AC: 8816 AN: 41494

American (AMR) AF: 0.0513 AC: 784 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1510 AN: 5182

South Asian (SAS) AF: 0.0395 AC: 190 AN: 4816

European-Finnish (FIN) AF: 0.0624 AC: 662 AN: 10612

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0203 AC: 1382 AN: 68014

Other (OTH) AF: 0.0718 AC: 152 AN: 2116

Alfa AF: 0.0209 Hom.: 27

Bravo AF: 0.0983

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.76
DANN	Benign	0.73
PhyloP100		-0.66
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: rs11581557; hg19: chr1-40328458;