4-156970811-C-A

Variant names:

• chr4-156970811-C-A
• rs149931440
• NM_016205.3:c.93G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016205.3(PDGFC):​c.93G>T​(p.Gln31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,611,858 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q31R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (15 hom.)
• Consequence: PDGFC NM_016205.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.82
• Publications: 13 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040890574).
• BP6: Variant 4-156970811-C-A is Benign according to our data. Variant chr4-156970811-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3050723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 470 AD gene.

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.93G>T	p.Gln31His	missense	Exon 1 of 6	NP_057289.1	Q9NRA1-1
	PDGFC	NR_036641.2		n.989G>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFC	ENST00000502773.6	TSL:1 MANE Select	c.93G>T	p.Gln31His	missense	Exon 1 of 6	ENSP00000422464.1	Q9NRA1-1
	PDGFC	ENST00000274071.6	TSL:1	n.93G>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000274071.2	J3KN71
	PDGFC	ENST00000954544.1		c.93G>T	p.Gln31His	missense	Exon 1 of 6	ENSP00000624603.1

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 470 AN: 152162 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00548

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00276 AC: 693 AN: 251442 AF XY: 0.00269

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00484

Gnomad FIN exome AF: 0.00245

Gnomad NFE exome AF: 0.00427

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00405 AC: 5914 AN: 1459578 Hom.: 15 Cov.: 30 AF XY: 0.00408 AC XY: 2965 AN XY: 726286

African (AFR) AF: 0.000419 AC: 14 AN: 33420

American (AMR) AF: 0.000581 AC: 26 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26124

East Asian (EAS) AF: 0.00675 AC: 268 AN: 39686

South Asian (SAS) AF: 0.000835 AC: 72 AN: 86226

European-Finnish (FIN) AF: 0.00264 AC: 141 AN: 53418

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.00463 AC: 5134 AN: 1109914

Other (OTH) AF: 0.00403 AC: 243 AN: 60308

GnomAD4 genome AF: 0.00309 AC: 470 AN: 152280 Hom.: 1 Cov.: 32 AF XY: 0.00271 AC XY: 202 AN XY: 74432

African (AFR) AF: 0.000602 AC: 25 AN: 41562

American (AMR) AF: 0.000719 AC: 11 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5168

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00548 AC: 373 AN: 68026

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00415 Hom.: 3

Bravo AF: 0.00284

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00407 AC: 35

ExAC AF: 0.00282 AC: 342

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00414

EpiControl AF: 0.00421

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PDGFC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.60
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.094
Sift	Benign	0.22	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.30		Loss of sheet (P = 0.0043)
MVP		0.18
MPC		0.29
ClinPred		0.012	T
GERP RS		5.1
PromoterAI		-0.0098	Neutral
Varity_R		0.17
gMVP		0.47
Mutation Taster		=89/11	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

dbSNP: rs149931440; hg19: chr4-157891963; COSMIC: COSV56849125; COSMIC: COSV56849125;