9-133463535-T-G

Variant names:

• chr9-133463535-T-G
• rs3124765
• NM_017586.5:c.174T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017586.5(CACFD1):​c.174T>G​(p.Ile58Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00672 in 1,613,976 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0053 (6 hom., cov: 34)
  • Exomes 𝑓: 0.0069 (43 hom.)
• Consequence: CACFD1 NM_017586.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 37 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.056706637).
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACFD1	NM_017586.5	MANE Select	c.174T>G	p.Ile58Met	missense	Exon 2 of 5	NP_060056.1
	CACFD1	NM_001242369.2		c.174T>G	p.Ile58Met	missense	Exon 2 of 6	NP_001229298.1
	CACFD1	NM_001242370.2		c.174T>G	p.Ile58Met	missense	Exon 2 of 5	NP_001229299.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACFD1	ENST00000316948.9	TSL:1 MANE Select	c.174T>G	p.Ile58Met	missense	Exon 2 of 5	ENSP00000317121.4
	CACFD1	ENST00000540581.5	TSL:2	c.174T>G	p.Ile58Met	missense	Exon 2 of 6	ENSP00000440832.1
	CACFD1	ENST00000542192.5	TSL:2	c.174T>G	p.Ile58Met	missense	Exon 2 of 5	ENSP00000444328.1

Frequencies

GnomAD3 genomes AF: 0.00529 AC: 805 AN: 152148 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00744

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00709

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00601 AC: 1511 AN: 251380 AF XY: 0.00633

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.00697

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00686 AC: 10032 AN: 1461710 Hom.: 43 Cov.: 49 AF XY: 0.00698 AC XY: 5072 AN XY: 727152

African (AFR) AF: 0.00117 AC: 39 AN: 33474

American (AMR) AF: 0.00190 AC: 85 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00275 AC: 72 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00874 AC: 754 AN: 86258

European-Finnish (FIN) AF: 0.0129 AC: 687 AN: 53304

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5766

European-Non Finnish (NFE) AF: 0.00716 AC: 7963 AN: 1111960

Other (OTH) AF: 0.00667 AC: 403 AN: 60390

GnomAD4 genome AF: 0.00529 AC: 806 AN: 152266 Hom.: 6 Cov.: 34 AF XY: 0.00579 AC XY: 431 AN XY: 74452

African (AFR) AF: 0.00116 AC: 48 AN: 41532

American (AMR) AF: 0.00333 AC: 51 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00786 AC: 38 AN: 4832

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00709 AC: 482 AN: 68018

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.0983 Hom.: 33083

TwinsUK AF: 0.00917 AC: 34

ALSPAC AF: 0.00701 AC: 27

ExAC AF: 0.00593 AC: 720

EpiCase AF: 0.00627

EpiControl AF: 0.00652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	7.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.057	T
MetaSVM	Uncertain	0.25	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		-2.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.40
Sift	Benign	0.092	T
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.81
MVP		0.29
MPC		0.56
ClinPred		0.051	T
GERP RS		-2.6
Varity_R		0.12
gMVP		0.86
Mutation Taster		=94/6	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: rs3124765; hg19: chr9-136328657;