Variant 4-156970811-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 15 hom. )

Consequence

PDGFC
NM_016205.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.82

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]

PDGFC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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 id is 3050723.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 470 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFC	NM_016205.3 linkuse as main transcript	c.93G>T	p.Gln31His	missense_variant	1/6	ENST00000502773.6
PDGFC	NR_036641.2 linkuse as main transcript	n.989G>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFC	ENST00000502773.6 linkuse as main transcript	c.93G>T	p.Gln31His	missense_variant	1/6	1	NM_016205.3	P1	Q9NRA1-1
PDGFC	ENST00000274071.6 linkuse as main transcript	c.93G>T	p.Gln31His	missense_variant, NMD_transcript_variant	1/7	1
PDGFC	ENST00000422544.2 linkuse as main transcript	c.93G>T	p.Gln31His	missense_variant	1/6	5			Q9NRA1-2
PDGFC	ENST00000513664.1 linkuse as main transcript	n.155G>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

470

AN:

152162

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00276

AC:

693

AN:

251442

Hom.:

AF XY:

0.00269

AC XY:

365

AN XY:

135908

show subpopulations

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 SAS exome

AF:

0.000588

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.:

Cov.:

AF XY:

0.00408

AC XY:

2965

AN XY:

726286

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.00675

Gnomad4 SAS exome

AF:

0.000835

Gnomad4 FIN exome

AF:

0.00264

Gnomad4 NFE exome

AF:

0.00463

Gnomad4 OTH exome

AF:

0.00403

GnomAD4 genome

AF:

0.00309

AC:

470

AN:

152280

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00464

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00548

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00416

Hom.:

Bravo

AF:

0.00284

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00282

AC:

342

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00421

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PDGFC-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 13, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.094

Sift

Benign

0.22

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0

B;.

Vest4

0.13

MutPred

0.30

Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);

MVP

0.18

MPC

0.29

ClinPred

0.012

GERP RS

5.1

Varity_R

0.17

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over