rs397514583
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_001866.3(COX7B):c.196del(p.Leu66CysfsTer48) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 23)
Consequence
COX7B
NM_001866.3 frameshift
NM_001866.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.37
Genes affected
COX7B (HGNC:2291): (cytochrome c oxidase subunit 7B) Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes subunit VIIb, which is highly similar to bovine COX VIIb protein and is found in all tissues. This gene may have several pseudogenes on chromosomes 1, 2, 20 and 22. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.198 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-77905212-AC-A is Pathogenic according to our data. Variant chrX-77905212-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 39767.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COX7B | NM_001866.3 | c.196del | p.Leu66CysfsTer48 | frameshift_variant | 3/3 | ENST00000650309.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COX7B | ENST00000650309.2 | c.196del | p.Leu66CysfsTer48 | frameshift_variant | 3/3 | NM_001866.3 | P1 | ||
COX7B | ENST00000373335.4 | c.136del | p.Leu46CysfsTer48 | frameshift_variant | 4/4 | 2 | |||
COX7B | ENST00000647835.1 | c.*69del | 3_prime_UTR_variant | 3/3 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Linear skin defects with multiple congenital anomalies 2 Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 02, 2012 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at