chr9-133465392-G-A

Variant names:

• chr9-133465392-G-A
• NM_017586.5:c.265G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017586.5(CACFD1):​c.265G>A​(p.Val89Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V89E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CACFD1 NM_017586.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28379202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017586.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACFD1	NM_017586.5	MANE Select	c.265G>A	p.Val89Met	missense	Exon 3 of 5	NP_060056.1	Q9UGQ2-1
	CACFD1	NM_001242369.2		c.265G>A	p.Val89Met	missense	Exon 3 of 6	NP_001229298.1	Q9UGQ2-4
	CACFD1	NM_001242370.2		c.194+1837G>A		intron	N/A	NP_001229299.1	Q9UGQ2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACFD1	ENST00000316948.9	TSL:1 MANE Select	c.265G>A	p.Val89Met	missense	Exon 3 of 5	ENSP00000317121.4	Q9UGQ2-1
	CACFD1	ENST00000540581.5	TSL:2	c.265G>A	p.Val89Met	missense	Exon 3 of 6	ENSP00000440832.1	Q9UGQ2-4
	CACFD1	ENST00000877841.1		c.265G>A	p.Val89Met	missense	Exon 3 of 4	ENSP00000547900.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.3
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.13
Sift	Benign	0.048	D
Sift4G	Uncertain	0.037	D
Polyphen		0.45	P
Vest4		0.37
MutPred		0.53		Loss of ubiquitination at K92 (P = 0.1423)
MVP		0.14
MPC		0.33
ClinPred		0.88	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.058
gMVP		0.75
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

hg19: chr9-136330514;