Variant 9-133460167-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017586.5(CACFD1):c.101C>G(p.Ser34Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000428 in 1,402,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

CACFD1
NM_017586.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40

Variant links:

Genes affected

CACFD1 (HGNC:1365): (calcium channel flower domain containing 1) Predicted to be involved in vesicle-mediated transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CACFD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3968247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CACFD1	NM_017586.5 linkuse as main transcript	c.101C>G	p.Ser34Cys	missense_variant	1/5	ENST00000316948.9	NP_060056.1
CACFD1	NM_001242369.2 linkuse as main transcript	c.101C>G	p.Ser34Cys	missense_variant	1/6		NP_001229298.1
CACFD1	NM_001242370.2 linkuse as main transcript	c.101C>G	p.Ser34Cys	missense_variant	1/5		NP_001229299.1
CACFD1	NM_001135775.4 linkuse as main transcript	c.101C>G	p.Ser34Cys	missense_variant	1/4		NP_001129247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACFD1	ENST00000316948.9 linkuse as main transcript	c.101C>G	p.Ser34Cys	missense_variant	1/5	1	NM_017586.5	ENSP00000317121	P1	Q9UGQ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000428

AC:

AN:

1402940

Hom.:

Cov.:

AF XY:

0.00000433

AC XY:

AN XY:

692966

show subpopulations

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:

0.00000555

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.101C>G (p.S34C) alteration is located in exon 1 (coding exon 1) of the CACFD1 gene. This alteration results from a C to G substitution at nucleotide position 101, causing the serine (S) at amino acid position 34 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.016

.;.;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.033

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Pathogenic

0.65

MetaRNN

Benign

0.40

T;T;T;T

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

0.0

N;N;N;N

MutationTaster

Benign

0.74

D;D;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.33

N;N;N;N

REVEL

Benign

0.094

Sift

Uncertain

0.014

D;D;T;T

Sift4G

Uncertain

0.013

D;T;D;D

Polyphen

0.51, 0.027

.;.;P;B

Vest4

0.31

MutPred

0.57

Loss of glycosylation at S34 (P = 0.0537);Loss of glycosylation at S34 (P = 0.0537);Loss of glycosylation at S34 (P = 0.0537);Loss of glycosylation at S34 (P = 0.0537);

MVP

0.51

MPC

0.17

ClinPred

0.68

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.18

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over