rs863223294

Positions:

• chrX-49215240-TGACGC-TCCA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001256789.3(CACNA1F):​c.3439-1_3442delGCGTCinsTGG​(p.Arg1147fs) variant causes a frameshift, splice acceptor, missense, splice region, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 22)
• Consequence: CACNA1F NM_001256789.3 frameshift, splice_acceptor, missense, splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.92

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]

ACMG classification

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-49215241-GACGC-CCA is Pathogenic according to our data. Variant chrX-49215241-GACGC-CCA is described in ClinVar as [Pathogenic]. Clinvar id is 11620.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1F	NM_001256789.3	c.3439-1_3442delGCGTCinsTGG	p.Arg1147fs	frameshift_variant, splice_acceptor_variant, missense_variant, splice_region_variant, intron_variant	29/48	ENST00000323022.10	NP_001243718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1F	ENST00000323022.10	c.3439-1_3442delGCGTCinsTGG	p.Arg1147fs	frameshift_variant, splice_acceptor_variant, missense_variant, splice_region_variant, intron_variant	29/48	1	NM_001256789.3	ENSP00000321618.6
CACNA1F	ENST00000376265.2	c.3472-1_3475delGCGTCinsTGG	p.Arg1158fs	frameshift_variant, splice_acceptor_variant, missense_variant, splice_region_variant, intron_variant	29/48	1		ENSP00000365441.2
CACNA1F	ENST00000376251.5	c.3277-1_3280delGCGTCinsTGG	p.Arg1093fs	frameshift_variant, splice_acceptor_variant, missense_variant, splice_region_variant, intron_variant	29/48	1		ENSP00000365427.1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

X-linked cone-rod dystrophy 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs863223294; hg19: chrX-49071701;