Genetic Variant FDCSP:p.Pro52Ser (chr4-70234083-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152997.4(FDCSP):c.154C>T(p.Pro52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,611,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P52L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FDCSP
NM_152997.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22

Publications

0 publications found

Variant links:

Genes affected

FDCSP (HGNC:19215): (follicular dendritic cell secreted protein) This gene encodes a small secreted protein that is expressed in follicular dendritic cells. This protein specifically binds to activated B cells, and functions as a regulator of antibody responses. It is also thought to contribute to tumor metastases by promoting cancer cell migration and invasion. [provided by RefSeq, Dec 2011]

FDCSP links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12016404).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152997.4. 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
	FDCSP	NM_152997.4	MANE Select	c.154C>T	p.Pro52Ser	missense	Exon 4 of 5	NP_694542.1	Q8NFU4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDCSP	ENST00000317987.6	TSL:1 MANE Select	c.154C>T	p.Pro52Ser	missense	Exon 4 of 5	ENSP00000318437.5	Q8NFU4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151466

Hom.:

Cov.:

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:

0.0000148

Gnomad OTH

AF:

0.000482

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1459740

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33290

American (AMR)

AF:

0.00

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26022

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000225

AC:

AN:

1110572

Other (OTH)

AF:

0.0000166

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151466

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73938

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41326

American (AMR)

AF:

0.00

AC:

AN:

15134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67680

Other (OTH)

AF:

0.000482

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.2

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.17

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.43

M_CAP

Benign

0.0055

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

PhyloP100

-1.2

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.094

Sift

Pathogenic

0.0

Sift4G

Benign

0.60

Polyphen

0.058

Vest4

0.14

MutPred

0.12

Loss of catalytic residue at P52 (P = 0.0059)

MVP

0.040

MPC

0.16

ClinPred

0.41

GERP RS

-5.2

Varity_R

0.24

gMVP

0.11

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over