chr14-74946255-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002632.6(PGF):c.443G>A(p.Gly148Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,614,096 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 2 hom. )
Consequence
PGF
NM_002632.6 missense
NM_002632.6 missense
Scores
4
12
Clinical Significance
Conservation
PhyloP100: 3.27
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.011667907).
BS2
High AC in GnomAd4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGF | NM_002632.6 | c.443G>A | p.Gly148Glu | missense_variant | 6/7 | ENST00000555567.6 | |
LOC107984690 | XR_001750826.3 | n.2720C>T | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGF | ENST00000555567.6 | c.443G>A | p.Gly148Glu | missense_variant | 6/7 | 1 | NM_002632.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152244Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000259 AC: 65AN: 251436Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135902
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GnomAD4 exome AF: 0.000116 AC: 169AN: 1461852Hom.: 2 Cov.: 33 AF XY: 0.000128 AC XY: 93AN XY: 727238
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74368
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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 | Jan 23, 2023 | The c.443G>A (p.G148E) alteration is located in exon 6 (coding exon 6) of the PGF gene. This alteration results from a G to A substitution at nucleotide position 443, causing the glycine (G) at amino acid position 148 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.94
.;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at