NR_183424.1:n.272+254_272+255dupTT

Variant names:

• chr1-39883663-C-CTT
• rs58870544
• NR_183424.1:n.272+254_272+255dupTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NR_183424.1(MYCL-AS1):​n.272+254_272+255dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 146,222 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00034 (0 hom., cov: 30)
• Consequence: MYCL-AS1 NR_183424.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.796

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIT1	NM_017646.6	c.-174_-173dupAA		upstream_gene_variant		ENST00000316891.10	NP_060116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIT1	ENST00000316891.10	c.-173_-172insAA		upstream_gene_variant		1	NM_017646.6	ENSP00000321810.5
TRIT1	ENST00000372818.5	c.-173_-172insAA		upstream_gene_variant		1		ENSP00000361905.1
TRIT1	ENST00000462797.5	n.-173_-172insAA		upstream_gene_variant		5		ENSP00000473773.1
TRIT1	ENST00000486825.6	n.-191_-190insAA		upstream_gene_variant		5		ENSP00000474151.1
TRIT1	ENST00000489945.5	n.-173_-172insAA		upstream_gene_variant		5		ENSP00000473745.1
TRIT1	ENST00000492612.6	n.-185_-184insAA		upstream_gene_variant		5		ENSP00000473708.1

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 49 AN: 146186 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000339

Gnomad ASJ AF: 0.00676

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000272

Gnomad OTH AF: 0.00101

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

GnomAD4 genome AF: 0.000335 AC: 49 AN: 146222 Hom.: 0 Cov.: 30 AF XY: 0.000295 AC XY: 21 AN XY: 71120

Gnomad4 AFR AF: 0.0000249

Gnomad4 AMR AF: 0.000339

Gnomad4 ASJ AF: 0.00676

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000272

Gnomad4 OTH AF: 0.00100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58870544; hg19: chr1-40349335;