1-52687970-C-A

Variant names:

• chr1-52687970-C-A
• rs1558102448
• NM_023077.3:c.446G>T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_023077.3(COA7):​c.446G>T​(p.Ser149Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. S149S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COA7 NM_023077.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.94

Genes affected

COA7 (HGNC:25716): (cytochrome c oxidase assembly factor 7) Located in mitochondrial intermembrane space and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917
• PP5: Variant 1-52687970-C-A is Pathogenic according to our data. Variant chr1-52687970-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 625459.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COA7	NM_023077.3	c.446G>T	p.Ser149Ile	missense_variant	Exon 3 of 3	ENST00000371538.5	NP_075565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COA7	ENST00000371538.5	c.446G>T	p.Ser149Ile	missense_variant	Exon 3 of 3	1	NM_023077.3	ENSP00000360593.3
COA7	ENST00000486918.1	n.500G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 Pathogenic:1

Apr 15, 2019

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.71		Loss of catalytic residue at S149 (P = 0.0404);
MVP		0.86
MPC		0.69
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.62
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1558102448; hg19: chr1-53153642;