rs1556423369

Positions:

• chrM-7965-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000361739.1(MT-CO2):​c.380T>C​(p.Phe127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 1)
• Consequence: MT-CO2 ENST00000361739.1 missense
• Scores: Apogee2 Benign 0.086
• Clinical Significance: Uncertain significance no assertion criteria provided U:1 Hepatic-failure-/-COX-deficiency
• Conservation: PhyloP100: 3.45

Genes affected

COX2 (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP4: Apogee2 supports a benign effect, 0.08594062 < 0.5 .

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX2	COX2.1	c.380T>C	p.Phe127Ser	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-CO2	ENST00000361739.1	c.380T>C	p.Phe127Ser	missense_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0 AC: 1

Gnomad homoplasmic AF: 0.000018 AC: 1 AN: 56428

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56428

Alfa AF: 0.000223 Hom.: 0

Mitomap

Hepatic-failure-/-COX-deficiency

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial complex IV deficiency, nuclear type 1 Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Bodamer Research Lab, Boston Children's Hospital

Mar 29, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.086
Hmtvar	Pathogenic	0.65
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.36	T
DEOGEN2	Benign	0.0015	T
LIST_S2	Benign	0.54	T
MutationAssessor	Benign	-1.1	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	2.3	N
Sift	Benign	0.23	T
Sift4G	Uncertain	0.020	D
GERP RS		2.4
Varity_R		0.15

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556423369; hg19: chrM-7966;