4-156767853-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016205.3(PDGFC):​c.841G>A​(p.Gly281Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PDGFC
NM_016205.3 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12
Variant links:
Genes affected
PDGFC (HGNC:8801): (platelet derived growth factor C) The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factors for cells of mesenchymal origin and are characterized by a core motif of eight cysteines. This gene product appears to form only homodimers. It differs from the platelet-derived growth factor alpha and beta polypeptides in having an unusual N-terminal domain, the CUB domain. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDGFCNM_016205.3 linkuse as main transcriptc.841G>A p.Gly281Ser missense_variant 5/6 ENST00000502773.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDGFCENST00000502773.6 linkuse as main transcriptc.841G>A p.Gly281Ser missense_variant 5/61 NM_016205.3 P1Q9NRA1-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151982
Hom.:
0
Cov.:
32
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:
0.000193
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
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251114
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135698
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
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:
0.00000479
AC:
7
AN:
1461350
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726978
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
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:
0.00000657
AC:
1
AN:
152100
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 09, 2024The c.841G>A (p.G281S) alteration is located in exon 5 (coding exon 5) of the PDGFC gene. This alteration results from a G to A substitution at nucleotide position 841, causing the glycine (G) at amino acid position 281 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
0.30
BayesDel_addAF
Benign
-0.041
T
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.88
D
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.026
D
MetaRNN
Uncertain
0.72
D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-3.4
D
REVEL
Uncertain
0.53
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.53
MutPred
0.86
Gain of catalytic residue at G281 (P = 0.0843);
MVP
0.42
MPC
0.62
ClinPred
0.86
D
GERP RS
5.3
Varity_R
0.83
gMVP
0.94

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.

Other links and lift over

dbSNP: rs756815335; hg19: chr4-157689005; API