Variant 14-74948514-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002632.6(PGF):c.385G>A(p.Glu129Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000195 in 1,591,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

PGF
NM_002632.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

Variant links:

Genes affected

PGF (HGNC:8893): (placental growth factor) Enables growth factor activity. Involved in positive regulation of cell population proliferation. Predicted to be located in extracellular region. Predicted to be active in extracellular space. Implicated in several diseases, including brain ischemia; diabetic neuropathy; glioblastoma; myocardial infarction; and pancreatic endocrine carcinoma. Biomarker of several diseases, including artery disease (multiple); autoimmune disease of musculoskeletal system (multiple); epilepsy (multiple); limited scleroderma; and pancreatic endocrine carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

PGF links:

LOC107984690 (HGNC:):

LOC107984690 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGF	NM_002632.6 linkuse as main transcript	c.385G>A	p.Glu129Lys	missense_variant	4/7	ENST00000555567.6
LOC107984690	XR_001750826.3 linkuse as main transcript	n.4979C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGF	ENST00000555567.6 linkuse as main transcript	c.385G>A	p.Glu129Lys	missense_variant	4/7	1	NM_002632.6	P4	P49763-3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246338

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133346

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.0000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000167

AC:

AN:

1439322

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

712594

show subpopulations

Gnomad4 AFR exome

AF:

0.0000910

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000137

Gnomad4 OTH exome

AF:

0.0000843

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2023

The c.385G>A (p.E129K) alteration is located in exon 4 (coding exon 4) of the PGF gene. This alteration results from a G to A substitution at nucleotide position 385, causing the glutamic acid (E) at amino acid position 129 to be replaced by a lysine (K). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.22

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.15

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.68

D;D;D;D

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.8

L;L;.;L

MutationTaster

Benign

0.58

D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

D;D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

D;D;D;T

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.99, 0.98, 0.95

.;D;D;P

Vest4

0.67

MVP

0.33

MPC

0.35

ClinPred

0.73

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.43

gMVP

0.85

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