Variant X-47626062-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM5BP4_Moderate

The NM_001145252.3(CFP):c.1240T>C(p.Tyr414His) variant causes a missense change. The variant allele was found at a frequency of 0.00000513 in 1,170,701 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts 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. Y414D) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000019 ( 0 hom. 0 hem. )

Consequence

CFP
NM_001145252.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.29

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chrX-47626062-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 11185.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.23068368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFP	NM_001145252.3 linkuse as main transcript	c.1240T>C	p.Tyr414His	missense_variant	8/9	ENST00000396992.8
CFP	NM_002621.2 linkuse as main transcript	c.1240T>C	p.Tyr414His	missense_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFP	ENST00000396992.8 linkuse as main transcript	c.1240T>C	p.Tyr414His	missense_variant	8/9	1	NM_001145252.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000360

AC:

AN:

111088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33294

show subpopulations

Gnomad AFR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000189

AC:

AN:

1059613

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

344781

show subpopulations

Gnomad4 AFR exome

AF:

0.0000785

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000360

AC:

AN:

111088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33294

show subpopulations

Gnomad4 AFR

AF:

0.000131

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T

FATHMM_MKL

Uncertain

0.86

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.5

L;L;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.13

T;T;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.93

P;P;.

Vest4

0.28

MutPred

0.47

Gain of ubiquitination at K413 (P = 0.0597);Gain of ubiquitination at K413 (P = 0.0597);Gain of ubiquitination at K413 (P = 0.0597);

MVP

0.29

MPC

1.9

ClinPred

0.83

GERP RS

5.5

Varity_R

0.35

gMVP

0.81

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