Variant X-49205192-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001256789.3(CACNA1F):c.5846C>T(p.Ser1949Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000984 in 1,209,412 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 35 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. S1949S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000096 ( 0 hom. 31 hem. )

Consequence

CACNA1F
NM_001256789.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023823678).

BP6

Variant X-49205192-G-A is Benign according to our data. Variant chrX-49205192-G-A is described in ClinVar as [Benign]. Clinvar id is 1168361.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1F	NM_001256789.3 linkuse as main transcript	c.5846C>T	p.Ser1949Phe	missense_variant	48/48	ENST00000323022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1F	ENST00000323022.10 linkuse as main transcript	c.5846C>T	p.Ser1949Phe	missense_variant	48/48	1	NM_001256789.3		O60840-2
CACNA1F	ENST00000376265.2 linkuse as main transcript	c.5879C>T	p.Ser1960Phe	missense_variant	48/48	1		P1	O60840-1
CACNA1F	ENST00000376251.5 linkuse as main transcript	c.5684C>T	p.Ser1895Phe	missense_variant	48/48	1			O60840-4

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

112066

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34216

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00414

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000220

AC:

AN:

182123

Hom.:

AF XY:

0.000224

AC XY:

AN XY:

66827

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00483

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000957

AC:

105

AN:

1097346

Hom.:

Cov.:

AF XY:

0.0000855

AC XY:

AN XY:

362750

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00433

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000713

Gnomad4 OTH exome

AF:

0.000326

GnomAD4 genome

AF:

0.000125

AC:

AN:

112066

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34216

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00414

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000651

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Uncertain

-0.050

Cadd

Uncertain

Dann

Uncertain

1.0

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.85

D;D;D

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Uncertain

0.61

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.015

D;T;T

Sift4G

Uncertain

0.045

D;D;T

Polyphen

0.93

.;.;P

Vest4

0.27

MVP

0.86

MPC

0.26

ClinPred

0.13

GERP RS

5.0

Varity_R

0.23

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

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