rs1557109796
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001256789.3(CACNA1F):c.1505_1509delGAGCC(p.Arg502fs) 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 Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
CACNA1F
NM_001256789.3 frameshift
NM_001256789.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.18
Genes affected
CACNA1F (HGNC:1393): (calcium voltage-gated channel subunit alpha1 F) This gene encodes a multipass transmembrane protein that functions as an alpha-1 subunit of the voltage-dependent calcium channel, which mediates the influx of calcium ions into the cell. The encoded protein forms a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Mutations in this gene can cause X-linked eye disorders, including congenital stationary night blindness type 2A, cone-rod dystropy, and Aland Island eye disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-49226050-TGGCTC-T is Pathogenic according to our data. Variant chrX-49226050-TGGCTC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438121.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-49226050-TGGCTC-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1F | NM_001256789.3 | c.1505_1509delGAGCC | p.Arg502fs | frameshift_variant | 13/48 | ENST00000323022.10 | NP_001243718.1 | |
CACNA1F | NM_005183.4 | c.1538_1542delGAGCC | p.Arg513fs | frameshift_variant | 13/48 | NP_005174.2 | ||
CACNA1F | NM_001256790.3 | c.1343_1347delGAGCC | p.Arg448fs | frameshift_variant | 13/48 | NP_001243719.1 | ||
CACNA1F | XM_011543983.3 | c.1343_1347delGAGCC | p.Arg448fs | frameshift_variant | 13/47 | XP_011542285.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1F | ENST00000323022.10 | c.1505_1509delGAGCC | p.Arg502fs | frameshift_variant | 13/48 | 1 | NM_001256789.3 | ENSP00000321618.6 | ||
CACNA1F | ENST00000376265.2 | c.1538_1542delGAGCC | p.Arg513fs | frameshift_variant | 13/48 | 1 | ENSP00000365441.2 | |||
CACNA1F | ENST00000376251.5 | c.1343_1347delGAGCC | p.Arg448fs | frameshift_variant | 13/48 | 1 | ENSP00000365427.1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital stationary night blindness Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at