4-70234074-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152997.4(FDCSP):​c.145C>T​(p.Pro49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FDCSP
NM_152997.4 missense

Scores

2
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.531
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15608966).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FDCSPNM_152997.4 linkc.145C>T p.Pro49Ser missense_variant Exon 4 of 5 ENST00000317987.6 NP_694542.1 Q8NFU4Q540F3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FDCSPENST00000317987.6 linkc.145C>T p.Pro49Ser missense_variant Exon 4 of 5 1 NM_152997.4 ENSP00000318437.5 Q8NFU4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250308
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135282
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000873
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1459364
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726020
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000672
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:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.145C>T (p.P49S) alteration is located in exon 4 (coding exon 3) of the FDCSP gene. This alteration results from a C to T substitution at nucleotide position 145, causing the proline (P) at amino acid position 49 to be replaced by a serine (S). 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
Benign
0.24
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.042
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.36
T
PROVEAN
Pathogenic
-7.4
D
REVEL
Benign
0.063
Sift
Benign
0.20
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.89
P
Vest4
0.28
MutPred
0.097
Loss of glycosylation at P47 (P = 0.1548);
MVP
0.11
MPC
0.16
ClinPred
0.53
D
GERP RS
3.3
Varity_R
0.091
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs775215113; hg19: chr4-71099791; COSMIC: COSV100525765; API