1-39883663-C-CTTTTT

Variant names:

• chr1-39883663-C-CTTTTT
• rs58870544
• ENST00000418255.2:n.325+479_325+480insTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000418255.2(MYCL-AS1):​n.325+479_325+480insTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MYCL-AS1 ENST00000418255.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.796
• Publications: 0 publications found

Genes affected

MYCL-AS1 (HGNC:40386): (MYCL antisense RNA 1)

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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418255.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCL-AS1	NR_183424.1		n.272+251_272+255dupTTTTT		intron	N/A
	MYCL-AS1	NR_183425.1		n.35+488_35+492dupTTTTT		intron	N/A
	TRIT1	NM_017646.6	MANE Select	c.-177_-173dupAAAAA		upstream_gene	N/A	NP_060116.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCL-AS1	ENST00000418255.2	TSL:2	n.325+479_325+480insTTTTT		intron	N/A
	MYCL-AS1	ENST00000837551.1		n.303+242_303+243insTTTTT		intron	N/A
	TRIT1	ENST00000316891.10	TSL:1 MANE Select	c.-173_-172insAAAAA		upstream_gene	N/A	ENSP00000321810.5	Q9H3H1-1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000706 Hom.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58870544; hg19: chr1-40349335;