Variant chrX-49230253-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001256789.3(CACNA1F):c.784C>T(p.Arg262Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

CACNA1F
NM_001256789.3 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 0.305

Variant links:

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]

CACNA1F links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 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-49230253-G-A is Pathogenic according to our data. Variant chrX-49230253-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 438128.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-49230253-G-A is described in Lovd as [Pathogenic]. Variant chrX-49230253-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CACNA1F	NM_001256789.3 linkuse as main transcript	c.784C>T	p.Arg262Ter	stop_gained	6/48	ENST00000323022.10	NP_001243718.1
CACNA1F	NM_005183.4 linkuse as main transcript	c.784C>T	p.Arg262Ter	stop_gained	6/48		NP_005174.2
CACNA1F	NM_001256790.3 linkuse as main transcript	c.589C>T	p.Arg197Ter	stop_gained	6/48		NP_001243719.1
CACNA1F	XM_011543983.3 linkuse as main transcript	c.589C>T	p.Arg197Ter	stop_gained	6/47		XP_011542285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1F	ENST00000323022.10 linkuse as main transcript	c.784C>T	p.Arg262Ter	stop_gained	6/48	1	NM_001256789.3	ENSP00000321618		O60840-2
CACNA1F	ENST00000376265.2 linkuse as main transcript	c.784C>T	p.Arg262Ter	stop_gained	6/48	1		ENSP00000365441	P1	O60840-1
CACNA1F	ENST00000376251.5 linkuse as main transcript	c.589C>T	p.Arg197Ter	stop_gained	6/48	1		ENSP00000365427		O60840-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1093243

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

359089

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2020

- -

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

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.74

BayesDel_noAF

Pathogenic

0.48

CADD

Pathogenic

DANN

Uncertain

1.0

FATHMM_MKL

Benign

0.28

MutationTaster

Benign

1.0

A;A;A

Vest4

0.93

GERP RS

4.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over