chr1-39883663-C-CT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000418255.2(MYCL-AS1):​n.325+479_325+480insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 146,096 control chromosomes in the GnomAD database, including 577 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.079 (577 hom., cov: 30)
• Consequence: MYCL-AS1 ENST00000418255.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-39883663-C-CT is Benign according to our data. Variant chr1-39883663-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1276471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 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+255dupT		intron	N/A
	MYCL-AS1	NR_183425.1		n.35+492dupT		intron	N/A
	TRIT1	NM_017646.6	MANE Select	c.-173dupA		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+480insT		intron	N/A
	MYCL-AS1	ENST00000837551.1		n.303+242_303+243insT		intron	N/A
	TRIT1	ENST00000316891.10	TSL:1 MANE Select	c.-173_-172insA		upstream_gene	N/A	ENSP00000321810.5	Q9H3H1-1

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 11581 AN: 146060 Hom.: 577 Cov.: 30

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0957

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00119

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0913

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0793 AC: 11579 AN: 146096 Hom.: 577 Cov.: 30 AF XY: 0.0777 AC XY: 5518 AN XY: 71038

African (AFR) AF: 0.0233 AC: 937 AN: 40170

American (AMR) AF: 0.0957 AC: 1409 AN: 14728

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 522 AN: 3400

East Asian (EAS) AF: 0.00119 AC: 6 AN: 5044

South Asian (SAS) AF: 0.119 AC: 541 AN: 4556

European-Finnish (FIN) AF: 0.0913 AC: 824 AN: 9024

Middle Eastern (MID) AF: 0.0870 AC: 24 AN: 276

European-Non Finnish (NFE) AF: 0.107 AC: 7060 AN: 66020

Other (OTH) AF: 0.0770 AC: 153 AN: 1986

Alfa AF: 0.0223 Hom.: 15

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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; COSMIC: COSV57547175;