Variant chr9-133463488-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_017586.5(CACFD1):c.127G>A(p.Ala43Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CACFD1
NM_017586.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.33

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACFD1	NM_017586.5 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	2/5	ENST00000316948.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACFD1	ENST00000316948.9 linkuse as main transcript	c.127G>A	p.Ala43Thr	missense_variant	2/5	1	NM_017586.5	P1	Q9UGQ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251374

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D;D;D;T

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.75

D;D;D;D;D

MetaSVM

Uncertain

0.37

MutationAssessor

Benign

1.8

L;L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.6

N;N;N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0080

D;T;T;T;T

Sift4G

Uncertain

0.012

D;D;D;T;D

Polyphen

1.0, 0.88

.;.;D;P;.

Vest4

0.66

MutPred

0.53

Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);.;

MVP

0.66

MPC

0.28

ClinPred

0.88

GERP RS

4.8

Varity_R

0.14

gMVP

0.76

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over