4-156763096-T-C

Position:

• chr4-156763096-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_016205.3(PDGFC):​c.1032A>G​(p.Gly344Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,567,192 control chromosomes in the GnomAD database, including 25,106 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2520 hom., cov: 31)
  • Exomes 𝑓: 0.17 (22586 hom.)
• Consequence: PDGFC NM_016205.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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]

PDGFC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=0.339 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFC	NM_016205.3	c.1032A>G	p.Gly344Gly	synonymous_variant	6/6	ENST00000502773.6	NP_057289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFC	ENST00000502773.6	c.1032A>G	p.Gly344Gly	synonymous_variant	6/6	1	NM_016205.3	ENSP00000422464.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26794 AN: 151910 Hom.: 2520 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0859

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.166

GnomAD3 exomes AF: 0.194 AC: 48620 AN: 250764 Hom.: 5511 AF XY: 0.202 AC XY: 27383 AN XY: 135516

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.172

Gnomad SAS exome AF: 0.388

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.168 AC: 237480 AN: 1415164 Hom.: 22586 Cov.: 26 AF XY: 0.174 AC XY: 123281 AN XY: 706936

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.176 AC: 26806 AN: 152028 Hom.: 2520 Cov.: 31 AF XY: 0.180 AC XY: 13380 AN XY: 74304

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.167

Alfa AF: 0.147 Hom.: 1250

Bravo AF: 0.172

Asia WGS AF: 0.274 AC: 950 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.8
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs3815861; hg19: chr4-157684248; COSMIC: COSV56845002; COSMIC: COSV56845002;