rs201950015

Variant names:

• chrM-7476-C-T
• rs201950015
• unassigned_transcript_4800:c.39G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

This summary comes from the ClinGen Evidence Repository: The m.7476C>T variant in MT-TS1 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID:32906214). This variant is seen in 1.310% of individuals in the GenBank dataset (BA1), including in haplogroups J2a (99.7% of individuals) and J2b (98.85% of individuals). Furthermore, this variant is seen in the gnomAD dataset (v3.1.2) at an overall homoplasmic allele frequency of 1% including in haplogroup J at 20%. If an affected individual is not a member this haplogroup, further evaluation of the variant in that particular individual should be considered. The computational predictor MitoTIP suggests this variant does not impact the function of this tRNA with a score in the 20th percentile, as does HmtVar with a score of 0.1 (BP4). In summary, this variant meets criteria to be classified as benign. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BA1, BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA131013/MONDO:0044970/014

• Frequency: Mitomap GenBank: 𝑓 0.013 (AC: 805)
• Consequence: TRNS1 unassigned_transcript_4800 synonymous
• Scores: Mitotip Benign 0.016
• Clinical Significance: Benign reviewed by expert panel B:3 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.836
• Publications: 8 publications found

Genes affected

TRNS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

MT-CO2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-CO1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

TRND (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

TRND Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387416.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-TS1	ENST00000387416.2	TSL:6	n.39G>A		non_coding_transcript_exon	Exon 1 of 1
	MT-CO2	ENST00000361739.1	TSL:6	c.-110C>T		upstream_gene	N/A	ENSP00000354876.1	P00403
	MT-CO1	ENST00000361624.2	TSL:6	c.*31C>T		downstream_gene	N/A	ENSP00000354499.2	P00395

Frequencies

Mitomap GenBank AF: 0.013 AC: 805

Gnomad homoplasmic AF: 0.011 AC: 622 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Alfa AF: 0.0133 Hom.: 617

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	1	MELAS syndrome (1)
-	-	1	Mitochondrial disease (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	0.016
Hmtvar	Benign	0.10
PhyloP100		-0.84

Other links and lift over

dbSNP: rs201950015; hg19: chrM-7477;