ENST00000418255.2:n.325+554T>C

Variant names:

• chr1-39883738-T-C
• rs7535397
• ENST00000418255.2:n.325+554T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000418255.2(MYCL-AS1):​n.325+554T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,554 control chromosomes in the GnomAD database, including 26,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.57 (26451 hom., cov: 29)
• Consequence: MYCL-AS1 ENST00000418255.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33
• Publications: 3 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-39883738-T-C is Benign according to our data. Variant chr1-39883738-T-C is described in ClinVar as Benign. ClinVar VariationId is 1274712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

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+317T>C		intron	N/A
	MYCL-AS1	NR_183425.1		n.35+554T>C		intron	N/A
	TRIT1	NM_017646.6	MANE Select	c.-247A>G		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+554T>C		intron	N/A
	MYCL-AS1	ENST00000837551.1		n.303+317T>C		intron	N/A
	TRIT1	ENST00000316891.10	TSL:1 MANE Select	c.-247A>G		upstream_gene	N/A	ENSP00000321810.5	Q9H3H1-1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85742 AN: 151436 Hom.: 26394 Cov.: 29

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.566 AC: 85850 AN: 151554 Hom.: 26451 Cov.: 29 AF XY: 0.564 AC XY: 41735 AN XY: 74042

African (AFR) AF: 0.830 AC: 34293 AN: 41298

American (AMR) AF: 0.488 AC: 7439 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1814 AN: 3464

East Asian (EAS) AF: 0.598 AC: 3080 AN: 5148

South Asian (SAS) AF: 0.479 AC: 2297 AN: 4794

European-Finnish (FIN) AF: 0.469 AC: 4915 AN: 10488

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30593 AN: 67820

Other (OTH) AF: 0.513 AC: 1083 AN: 2112

Alfa AF: 0.523 Hom.: 2765

Bravo AF: 0.581

Asia WGS AF: 0.587 AC: 2039 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.87
PhyloP100		-1.3
PromoterAI		0.0032	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7535397; hg19: chr1-40349410;