4-156763112-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_016205.3(PDGFC):​c.1016G>A​(p.Cys339Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PDGFC
NM_016205.3 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDGFCNM_016205.3 linkc.1016G>A p.Cys339Tyr missense_variant Exon 6 of 6 ENST00000502773.6 NP_057289.1 Q9NRA1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDGFCENST00000502773.6 linkc.1016G>A p.Cys339Tyr missense_variant Exon 6 of 6 1 NM_016205.3 ENSP00000422464.1 Q9NRA1-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.89e-7
AC:
1
AN:
1450460
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
722354
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1016G>A (p.C339Y) alteration is located in exon 6 (coding exon 6) of the PDGFC gene. This alteration results from a G to A substitution at nucleotide position 1016, causing the cysteine (C) at amino acid position 339 to be replaced by a tyrosine (Y). 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
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.74
D;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.067
D
MetaRNN
Pathogenic
0.77
D;D
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-5.0
D;D
REVEL
Pathogenic
0.65
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.91
MutPred
0.45
Gain of phosphorylation at C339 (P = 0.0297);.;
MVP
0.63
MPC
1.4
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.85
gMVP
1.0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-157684264; COSMIC: COSV56851231; COSMIC: COSV56851231; API