NM_016205.3:c.92A>G

Variant names:

• chr4-156970812-T-C
• NM_016205.3:c.92A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016205.3(PDGFC):​c.92A>G​(p.Gln31Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q31H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDGFC NM_016205.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.95

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]

ACMG classification

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=0.10791585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFC	NM_016205.3	c.92A>G	p.Gln31Arg	missense_variant	Exon 1 of 6	ENST00000502773.6	NP_057289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFC	ENST00000502773.6	c.92A>G	p.Gln31Arg	missense_variant	Exon 1 of 6	1	NM_016205.3	ENSP00000422464.1
PDGFC	ENST00000274071.6	n.92A>G		non_coding_transcript_exon_variant	Exon 1 of 7	1		ENSP00000274071.2
PDGFC	ENST00000422544.2	c.92A>G	p.Gln31Arg	missense_variant	Exon 1 of 6	5		ENSP00000410048.2
PDGFC	ENST00000513664.1	n.154A>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.92A>G (p.Q31R) alteration is located in exon 1 (coding exon 1) of the PDGFC gene. This alteration results from a A to G substitution at nucleotide position 92, causing the glutamine (Q) at amino acid position 31 to be replaced by an arginine (R). 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	0.091
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.55
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.070	N;N
REVEL	Benign	0.081
Sift	Benign	0.81	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.020	B;.
Vest4		0.23
MutPred		0.31		Gain of methylation at Q31 (P = 0.0296);Gain of methylation at Q31 (P = 0.0296);
MVP		0.38
MPC		0.34
ClinPred		0.12	T
GERP RS		5.1
Varity_R		0.19
gMVP		0.53

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: chr4-157891964;