4-156772747-A-T

Variant names:

• chr4-156772747-A-T
• NM_016205.3:c.642T>A

Variant summary

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

The NM_016205.3(PDGFC):​c.642T>A​(p.Asp214Glu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDGFC NM_016205.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0810
• Publications: 0 publications found

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

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=0.17321369).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016205.3. 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
	PDGFC	NM_016205.3	MANE Select	c.642T>A	p.Asp214Glu	missense	Exon 4 of 6	NP_057289.1	Q9NRA1-1
	PDGFC	NR_036641.2		n.1599T>A		non_coding_transcript_exon	Exon 5 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFC	ENST00000502773.6	TSL:1 MANE Select	c.642T>A	p.Asp214Glu	missense	Exon 4 of 6	ENSP00000422464.1	Q9NRA1-1
	PDGFC	ENST00000274071.6	TSL:1	n.*550T>A		non_coding_transcript_exon	Exon 5 of 7	ENSP00000274071.2	J3KN71
	PDGFC	ENST00000274071.6	TSL:1	n.*550T>A		3_prime_UTR	Exon 5 of 7	ENSP00000274071.2	J3KN71

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.081
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.14
Sift	Benign	0.20	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.52		Gain of helix (P = 0.0696)
MVP		0.093
MPC		0.29
ClinPred		0.17	T
GERP RS		-1.6
Varity_R		0.046
gMVP		0.40
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

hg19: chr4-157693899;