19-43258901-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002784.5(PSG9):c.944G>A(p.Arg315Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,587,404 control chromosomes in the GnomAD database, including 111 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00052 ( 6 hom., cov: 30)
Exomes 𝑓: 0.00067 ( 105 hom. )
Consequence
PSG9
NM_002784.5 missense
NM_002784.5 missense
Scores
15
Clinical Significance
Conservation
PhyloP100: 0.408
Genes affected
PSG9 (HGNC:9526): (pregnancy specific beta-1-glycoprotein 9) The protein encoded by this gene is a member of the pregnancy-specific glycoprotein (PSG) family. This protein family and the closely related carcinoembryonic antigen cell adhesion molecule (CEACAM) gene family are both members of the immunoglobulin superfamily, and are organized as a large gene cluster. This protein is thought to inhibit platelet-fibrinogen interactions. Several studies suggest that reduced serum concentrations of PSGs are associated with fetal growth restrictions, while up-regulation of this gene has been observed in colorectal cancers. Several pseudogenes of this gene are found on chromosome 19. Alternative splicing results in multiple transcript variants that encode multiple protein isoforms. [provided by RefSeq, Sep 2014]
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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=0.030593961).
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PSG9 | NM_002784.5 | c.944G>A | p.Arg315Gln | missense_variant | 4/6 | ENST00000270077.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PSG9 | ENST00000270077.8 | c.944G>A | p.Arg315Gln | missense_variant | 4/6 | 1 | NM_002784.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000523 AC: 76AN: 145370Hom.: 6 Cov.: 30
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GnomAD3 exomes AF: 0.000541 AC: 133AN: 245994Hom.: 13 AF XY: 0.000683 AC XY: 91AN XY: 133296
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GnomAD4 exome AF: 0.000674 AC: 972AN: 1441922Hom.: 105 Cov.: 34 AF XY: 0.000688 AC XY: 494AN XY: 717542
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GnomAD4 genome AF: 0.000522 AC: 76AN: 145482Hom.: 6 Cov.: 30 AF XY: 0.000437 AC XY: 31AN XY: 70968
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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 | Jun 17, 2022 | The c.944G>A (p.R315Q) alteration is located in exon 4 (coding exon 4) of the PSG9 gene. This alteration results from a G to A substitution at nucleotide position 944, causing the arginine (R) at amino acid position 315 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
Sift4G
Benign
T;T;T;T
Polyphen
0.027, 0.037
.;.;B;B
Vest4
MVP
MPC
0.0053
ClinPred
T
GERP RS
Varity_R
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