9-133460167-C-G

Position:

• chr9-133460167-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.40

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]

ACMG classification

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	UniProt
CACFD1	NM_017586.5	c.101C>G	p.Ser34Cys	missense_variant	1/5	ENST00000316948.9
CACFD1	NM_001242369.2	c.101C>G	p.Ser34Cys	missense_variant	1/6
CACFD1	NM_001242370.2	c.101C>G	p.Ser34Cys	missense_variant	1/5
CACFD1	NM_001135775.4	c.101C>G	p.Ser34Cys	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACFD1	ENST00000316948.9	c.101C>G	p.Ser34Cys	missense_variant	1/5	1	NM_017586.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000428 AC: 6 AN: 1402940 Hom.: 0 Cov.: 32 AF XY: 0.00000433 AC XY: 3 AN XY: 692966

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Benign	0.93
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.033
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	0.0	N;N;N;N
MutationTaster	Benign	0.74	D;D;N;N
PrimateAI	Uncertain	0.72	T
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	D
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.

Other links and lift over

hg19: chr9-136325289;