9-133467937-A-G

Variant names:

• chr9-133467937-A-G
• rs587770123
• NM_017586.5:c.337A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017586.5(CACFD1):​c.337A>G​(p.Ile113Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: CACFD1 NM_017586.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.245
• Publications: 1 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]

LOC124902295 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.027788013).

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.337A>G	p.Ile113Val	missense	Exon 4 of 5	NP_060056.1	Q9UGQ2-1
	CACFD1	NM_001242369.2		c.337A>G	p.Ile113Val	missense	Exon 4 of 6	NP_001229298.1	Q9UGQ2-4
	CACFD1	NM_001242370.2		c.211A>G	p.Ile71Val	missense	Exon 3 of 5	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.337A>G	p.Ile113Val	missense	Exon 4 of 5	ENSP00000317121.4	Q9UGQ2-1
	CACFD1	ENST00000540581.5	TSL:2	c.337A>G	p.Ile113Val	missense	Exon 4 of 6	ENSP00000440832.1	Q9UGQ2-4
	CACFD1	ENST00000542192.5	TSL:2	c.211A>G	p.Ile71Val	missense	Exon 3 of 5	ENSP00000444328.1	Q9UGQ2-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250882 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1460856 Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15 AN XY: 726778

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53056

Middle Eastern (MID) AF: 0.00113 AC: 6 AN: 5326

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111918

Other (OTH) AF: 0.0000663 AC: 4 AN: 60332

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74444

African (AFR) AF: 0.00 AC: 0 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000334 Hom.: 0

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.052
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.019
DANN	Benign	0.58
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.22	N
PhyloP100		0.24
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.031
Sift	Benign	0.24	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.59		Gain of catalytic residue at I113 (P = 0.0217)
MVP		0.040
MPC		0.12
ClinPred		0.036	T
GERP RS		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.017
gMVP		0.39
Mutation Taster		=84/16	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

dbSNP: rs587770123; hg19: chr9-136333059;