NM_001256789.3:c.5848C>G

Variant names:

• chrX-49205190-G-C
• NM_001256789.3:c.5848C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256789.3(CACNA1F):​c.5848C>G​(p.Arg1950Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,984 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: CACNA1F NM_001256789.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16559306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1F	NM_001256789.3	c.5848C>G	p.Arg1950Gly	missense_variant	Exon 48 of 48	ENST00000323022.10	NP_001243718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1F	ENST00000323022.10	c.5848C>G	p.Arg1950Gly	missense_variant	Exon 48 of 48	1	NM_001256789.3	ENSP00000321618.6
CACNA1F	ENST00000376265.2	c.5881C>G	p.Arg1961Gly	missense_variant	Exon 48 of 48	1		ENSP00000365441.2
CACNA1F	ENST00000376251.5	c.5686C>G	p.Arg1896Gly	missense_variant	Exon 48 of 48	1		ENSP00000365427.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096984 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362404

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.9
DANN	Benign	0.93
DEOGEN2	Benign	0.14	.;.;T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Uncertain	0.069	D
MutationAssessor	Benign	0.090	.;.;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0010	.;.;B
Vest4		0.16
MutPred		0.34		.;.;Gain of glycosylation at S1960 (P = 0.0271);
MVP		0.54
MPC		0.29
ClinPred		0.060	T
GERP RS		2.1
Varity_R		0.15
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-49061650;