4-70234032-G-C

Variant names:

• chr4-70234032-G-C
• rs146455356
• NM_152997.4:c.103G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152997.4(FDCSP):​c.103G>C​(p.Asp35His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. D35N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FDCSP NM_152997.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 2 publications found

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]

ACMG classification

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=0.18630287).

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.103G>C	p.Asp35His	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.103G>C	p.Asp35His	missense	Exon 4 of 5	ENSP00000318437.5	Q8NFU4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.83	T
PhyloP100		-1.2
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.080
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.15		Gain of glycosylation at S30 (P = 0.0046)
MVP		0.20
MPC		0.22
ClinPred		0.87	D
GERP RS		-1.7
Varity_R		0.70
gMVP		0.10
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs146455356; hg19: chr4-71099749;