17-9576742-T-G

Position:

• chr17-9576742-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_145054.5(CFAP52):​c.47T>G​(p.Leu16Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CFAP52 NM_145054.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.927

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP52	NM_145054.5	c.47T>G	p.Leu16Arg	missense_variant	1/14	ENST00000352665.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP52	ENST00000352665.10	c.47T>G	p.Leu16Arg	missense_variant	1/14	1	NM_145054.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Apr 08, 2024

The c.47T>G (p.L16R) alteration is located in exon 1 (coding exon 1) of the CFAP52 gene. This alteration results from a T to G substitution at nucleotide position 47, causing the leucine (L) at amino acid position 16 to be replaced by an arginine (R). 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	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	29
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	.;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.69	T;T;D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Benign	-0.37	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.20	N;D;.
REVEL	Uncertain	0.48
Sift	Benign	0.057	T;D;.
Sift4G	Benign	0.33	T;D;D
Polyphen		1.0	D;D;.
Vest4		0.94
MutPred		0.74		Loss of stability (P = 0.0264);Loss of stability (P = 0.0264);Loss of stability (P = 0.0264);
MVP		0.45
MPC		0.61
ClinPred		0.84	D
GERP RS		5.7
Varity_R		0.91
gMVP		0.87

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-9480059;