17-9576721-C-A

Variant names:

• chr17-9576721-C-A
• rs200153894
• NM_145054.5:c.26C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145054.5(CFAP52):​c.26C>A​(p.Ala9Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CFAP52 NM_145054.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• Publications: 0 publications found

Genes affected

CFAP52 (HGNC:16053): (cilia and flagella associated protein 52) WD repeat-containing proteins, such as WDR16, play crucial roles in a wide range of physiologic functions, including signal transduction, RNA processing, remodeling the cytoskeleton, regulation of vesicular traffic, and cell division (Silva et al., 2005 [PubMed 15967112]).[supplied by OMIM, Mar 2008]

STX8 (HGNC:11443): (syntaxin 8) The gene is a member of the syntaxin family. The encoded protein is involved in protein trafficking from early to late endosomes via vesicle fusion and exocytosis. A related pseudogene has been identified on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044321388).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145054.5. 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
	CFAP52	NM_145054.5	MANE Select	c.26C>A	p.Ala9Asp	missense	Exon 1 of 14	NP_659491.4
	CFAP52	NM_001080556.2		c.26C>A	p.Ala9Asp	missense	Exon 1 of 13	NP_001074025.1	Q8N1V2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP52	ENST00000352665.10	TSL:1 MANE Select	c.26C>A	p.Ala9Asp	missense	Exon 1 of 14	ENSP00000339449.5	Q8N1V2-1
	CFAP52	ENST00000396219.7	TSL:2	c.26C>A	p.Ala9Asp	missense	Exon 1 of 13	ENSP00000379521.3	Q8N1V2-3
	CFAP52	ENST00000576499.1	TSL:3	c.26C>A	p.Ala9Asp	missense	Exon 1 of 4	ENSP00000476293.1	V9GY13

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460050 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726286

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.00 AC: 0 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39512

South Asian (SAS) AF: 0.00 AC: 0 AN: 85888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111160

Other (OTH) AF: 0.0000166 AC: 1 AN: 60310

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.97
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Benign	0.16	T
Sift4G	Uncertain	0.033	D
Polyphen		0.0	B
Vest4		0.23
MutPred		0.51		Gain of methylation at K4 (P = 0.0686)
MVP		0.061
MPC		0.15
ClinPred		0.073	T
GERP RS		3.8
PromoterAI		-0.048	Neutral
Varity_R		0.10
gMVP		0.28
Mutation Taster		=100/0	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: rs200153894; hg19: chr17-9480038;