Variant X-47624426-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145252.3(CFP):c.1259T>C(p.Met420Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,207,342 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000026 ( 0 hom. 6 hem. )

Consequence

CFP
NM_001145252.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Variant links:

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 links:

ENSG00000283743 (HGNC:):

ENSG00000283743 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022216827).

BS2

High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFP	NM_001145252.3 link	c.1259T>C	p.Met420Thr	missense_variant	9/9	ENST00000396992.8	NP_001138724.1	P27918A0A0S2Z4I5
CFP	NM_002621.2 link	c.1259T>C	p.Met420Thr	missense_variant	10/10		NP_002612.1	P27918A0A0S2Z4I5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFP	ENST00000396992.8 link	c.1259T>C	p.Met420Thr	missense_variant	9/9	1	NM_001145252.3	ENSP00000380189.3		P27918

Frequencies

GnomAD3 genomes

AF:

0.00000908

AC:

AN:

110152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32490

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

182366

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66874

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1097190

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

362600

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000908

AC:

AN:

110152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32490

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.016

DANN

Benign

0.62

DEOGEN2

Benign

0.085

T;T

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.27

.;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.43

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.0020

Sift

Benign

0.62

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.0

B;B

Vest4

0.034

MVP

0.043

MPC

0.74

ClinPred

0.024

GERP RS

-6.2

Varity_R

0.14

gMVP

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over