rs1557109796

chrX-49226050-TGGCTC-T

Variant summary

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

The NM_001256789.3(CACNA1F):c.1505_1509del(p.Arg502GlnfsTer35) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. 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
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• 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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• 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	UniProt
CACNA1F	NM_001256789.3	c.1505_1509del	p.Arg502GlnfsTer35	frameshift_variant	13/48	ENST00000323022.10
CACNA1F	NM_001256790.3	c.1343_1347del	p.Arg448GlnfsTer35	frameshift_variant	13/48
CACNA1F	NM_005183.4	c.1538_1542del	p.Arg513GlnfsTer35	frameshift_variant	13/48
CACNA1F	XM_011543983.3	c.1343_1347del	p.Arg448GlnfsTer35	frameshift_variant	13/47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1F	ENST00000323022.10	c.1505_1509del	p.Arg502GlnfsTer35	frameshift_variant	13/48	1	NM_001256789.3
CACNA1F	ENST00000376251.5	c.1343_1347del	p.Arg448GlnfsTer35	frameshift_variant	13/48	1
CACNA1F	ENST00000376265.2	c.1538_1542del	p.Arg513GlnfsTer35	frameshift_variant	13/48	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

- -

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: rs1557109796; hg19: chrX-49082512;