rs1556423293

Positions:

• chrM-7472-A-C
• chrM-7472-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000387416.2(MT-TS1):​n.43T>G variant causes a non coding transcript exon 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: MT-TS1 ENST00000387416.2 non_coding_transcript_exon
• 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

Genes affected

MT-TS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))

TRNS1 (HGNC:):

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]

MT-TD (HGNC:7478): (mitochondrially encoded tRNA aspartic acid)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomadMitoHomoplasmic at 7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNS1	TRNS1.1	n.43T>G		non_coding_transcript_exon_variant	1/1
COX1	COX1.1			downstream_gene_variant			YP_003024028.1
TRND	TRND.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-TS1	ENST00000387416.2	n.43T>G		non_coding_transcript_exon_variant	1/1
MT-CO1	ENST00000361624.2			downstream_gene_variant				ENSP00000354499	P1
MT-TD	ENST00000387419.1			upstream_gene_variant

Frequencies

GnomAD4 exome Cov.: 0

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

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

MM-/-DMDF-modulator,PEM-/-AMDF-/-Motor-neuron-disease-like

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.4
Hmtvar	Pathogenic	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556423293; hg19: chrM-7473;