M-7471-C-T

Variant names:

• chrM-7471-C-T
• rs397515726
• unassigned_transcript_4800:c.44G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000000000(TRNS1):​c.44G>A​(p.Trp15*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 15)
• Consequence: TRNS1 ENST00000000000 stop_gained
• Scores: Mitotip Benign 2.6
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -3.33
• Publications: 0 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 -12 ACMG points.

• BP6: Variant M-7471-C-T is Benign according to our data. Variant chrM-7471-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 42225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 12

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNS1	unassigned_transcript_4800	c.44G>A	p.Trp15*	stop_gained	Exon 1 of 1
COX2	unassigned_transcript_4802	c.-115C>T		upstream_gene_variant
TRND	unassigned_transcript_4801	c.-47C>T		upstream_gene_variant
COX1	unassigned_transcript_4799	c.*26C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TS1	ENST00000387416.2	n.44G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-CO2	ENST00000361739.1	c.-115C>T		upstream_gene_variant		6		ENSP00000354876.1
MT-CO1	ENST00000361624.2	c.*26C>T		downstream_gene_variant		6		ENSP00000354499.2
MT-TD	ENST00000387419.1	n.-47C>T		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00020 AC: 15

Gnomad homoplasmic AF: 0.00021 AC: 12 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.000449 Hom.: 2

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 31, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

7471C>T in MTTS1: This variant is not expected to have clinical significance bec ause this variant has been found in the general population with haplogroup-speci fic frequencies ranging from 0.3% to 1.5% (http://www.mitomap.org). Additionally , this variant is reported as a branching polymorphism in phylogeny studies and belongs to H1ax mitochondrial haplogroup (Behar 2012). -

MELAS syndrome Benign:1

Jul 12, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.7471C>T variant in MT-TS1 gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.6
Hmtvar	Benign	0.10
PhyloP100		-3.3
Mutation Taster		=99/1	polymorphism

Other links and lift over

dbSNP: rs397515726; hg19: chrM-7472;