rs132630261

Variant names:

• chrX-47626062-A-C
• rs132630261
• NM_001145252.3:c.1240T>G

Your query was ambiguous. Multiple possible variants found:

• chrX-47626062-A-C
• chrX-47626062-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001145252.3(CFP):​c.1240T>G​(p.Tyr414Asp) 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: CFP NM_001145252.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.29
• Publications: 8 publications found

Genes affected

CFP (HGNC:8864): (complement factor properdin) This gene encodes a plasma glycoprotein that positively regulates the alternative complement pathway of the innate immune system. This protein binds to many microbial surfaces and apoptotic cells and stabilizes the C3- and C5-convertase enzyme complexes in a feedback loop that ultimately leads to formation of the membrane attack complex and lysis of the target cell. Mutations in this gene result in two forms of properdin deficiency, which results in high susceptibility to meningococcal infections. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Feb 2009]

CFP Gene-Disease associations (from GenCC):

• properdin deficiency, X-linked

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000283743 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832
• PP5: Variant X-47626062-A-C is Pathogenic according to our data. Variant chrX-47626062-A-C is described in ClinVar as Pathogenic. ClinVar VariationId is 11185.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFP	NM_001145252.3	c.1240T>G	p.Tyr414Asp	missense_variant	Exon 8 of 9	ENST00000396992.8	NP_001138724.1
CFP	NM_002621.2	c.1240T>G	p.Tyr414Asp	missense_variant	Exon 9 of 10		NP_002612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFP	ENST00000396992.8	c.1240T>G	p.Tyr414Asp	missense_variant	Exon 8 of 9	1	NM_001145252.3	ENSP00000380189.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Properdin deficiency, type III Pathogenic:1

Oct 15, 1996

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;D;T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.48	.;T;T
M_CAP	Uncertain	0.29	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	-0.050	T
MutationAssessor	Uncertain	2.2	M;M;.
PhyloP100		6.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0050	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.93	P;P;.
Vest4		0.39
MutPred		0.79		Gain of ubiquitination at K413 (P = 0.0261);Gain of ubiquitination at K413 (P = 0.0261);Gain of ubiquitination at K413 (P = 0.0261);
MVP		0.43
MPC		2.2
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.70
gMVP		0.93
Mutation Taster		=35/65	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs132630261; hg19: chrX-47485461;