rs1557109912

chrX-49226401-GCCCTCACAGGCAGCGTGTACAGCTGGCCAGAGCCCCCT-G

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_001256789.3(CACNA1F):c.1433_1463+7del variant causes a splice donor, splice donor 5th base, coding sequence, intron change. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. E478E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CACNA1F NM_001256789.3 splice_donor, splice_donor_5th_base, coding_sequence, intron
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.61

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 Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• PP5: Variant X-49226401-GCCCTCACAGGCAGCGTGTACAGCTGGCCAGAGCCCCCT-G is Pathogenic according to our data. Variant chrX-49226401-GCCCTCACAGGCAGCGTGTACAGCTGGCCAGAGCCCCCT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438120.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-49226401-GCCCTCACAGGCAGCGTGTACAGCTGGCCAGAGCCCCCT-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1F	NM_001256789.3	c.1433_1463+7del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	11/48	ENST00000323022.10
CACNA1F	NM_001256790.3	c.1271_1301+7del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	11/48
CACNA1F	NM_005183.4	c.1466_1496+7del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	11/48
CACNA1F	XM_011543983.3	c.1271_1301+7del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	11/47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1F	ENST00000323022.10	c.1433_1463+7del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	11/48	1	NM_001256789.3
CACNA1F	ENST00000376251.5	c.1271_1301+7del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	11/48	1
CACNA1F	ENST00000376265.2	c.1466_1496+7del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	11/48	1		P1

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

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

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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: rs1557109912; hg19: chrX-49082863;