rs1556423293

Variant names:

• chrM-7472-A-C
• rs1556423293
• unassigned_transcript_4800:c.43T>G

Your query was ambiguous. Multiple possible variants found:

• chrM-7472-A-C
• chrM-7472-A-G
• chrM-7472-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000000000(TRNS1):​c.43T>G​(p.Trp15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 10)
• Consequence: TRNS1 ENST00000000000 missense
• Scores: Mitotip Benign 2.4
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 MM-/-DMDF-modulator,PEM-/-AMDF-/-Motor-neuron-disease-like
• Conservation: PhyloP100: -0.563
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomadMitoHomoplasmic at 7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNS1	unassigned_transcript_4800	c.43T>G	p.Trp15Gly	missense_variant	Exon 1 of 1
COX2	unassigned_transcript_4802	c.-114A>C		upstream_gene_variant
TRND	unassigned_transcript_4801	c.-46A>C		upstream_gene_variant
COX1	unassigned_transcript_4799	c.*27A>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-TS1	ENST00000387416.2	n.43T>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-CO2	ENST00000361739.1	c.-114A>C		upstream_gene_variant		6		ENSP00000354876.1
MT-CO1	ENST00000361624.2	c.*27A>C		downstream_gene_variant		6		ENSP00000354499.2
MT-TD	ENST00000387419.1	n.-46A>C		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00020 AC: 10

Gnomad homoplasmic AF: 0.00012 AC: 7 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.000224 Hom.: 1

Mitomap

Disease(s): MM-/-DMDF-modulator,PEM-/-AMDF-/-Motor-neuron-disease-like

Status: Reported,See-7471insC

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 04, 2022

Mendelics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.4
Hmtvar	Pathogenic	0.80
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs1556423293; hg19: chrM-7473;