Variant chr19-43258901-C-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.408

Variant links:

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]

PSG9 links:

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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 linkuse as main transcript	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 linkuse as main transcript	c.944G>A	p.Arg315Gln	missense_variant	4/6	1	NM_002784.5	P2	Q00887-1

Frequencies

GnomAD3 genomes

AF:

0.000523

AC:

AN:

145370

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.00170

Gnomad SAS

AF:

0.000441

Gnomad FIN

AF:

0.0000962

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000536

Gnomad OTH

AF:

0.000502

GnomAD3 exomes

AF:

0.000541

AC:

133

AN:

245994

Hom.:

AF XY:

0.000683

AC XY:

AN XY:

133296

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.000590

Gnomad ASJ exome

AF:

0.000899

Gnomad EAS exome

AF:

0.000949

Gnomad SAS exome

AF:

0.000759

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000523

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

AF:

0.000674

AC:

972

AN:

1441922

Hom.:

105

Cov.:

AF XY:

0.000688

AC XY:

494

AN XY:

717542

show subpopulations

Gnomad4 AFR exome

AF:

0.000250

Gnomad4 AMR exome

AF:

0.000502

Gnomad4 ASJ exome

AF:

0.00100

Gnomad4 EAS exome

AF:

0.00557

Gnomad4 SAS exome

AF:

0.000799

Gnomad4 FIN exome

AF:

0.000114

Gnomad4 NFE exome

AF:

0.000553

Gnomad4 OTH exome

AF:

0.000744

GnomAD4 genome

AF:

0.000522

AC:

AN:

145482

Hom.:

Cov.:

AF XY:

0.000437

AC XY:

AN XY:

70968

show subpopulations

Gnomad4 AFR

AF:

0.000105

Gnomad4 AMR

AF:

0.00143

Gnomad4 ASJ

AF:

0.00117

Gnomad4 EAS

AF:

0.00171

Gnomad4 SAS

AF:

0.000441

Gnomad4 FIN

AF:

0.0000962

Gnomad4 NFE

AF:

0.000536

Gnomad4 OTH

AF:

0.000497

Alfa

AF:

0.000543

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000700

AC:

ExAC

AF:

0.000518

AC:

EpiCase

AF:

0.000329

EpiControl

AF:

0.000774

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.1

DANN

Benign

0.95

DEOGEN2

Benign

0.0044

T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.26

T;T;T;T

M_CAP

Benign

0.00062

MetaRNN

Benign

0.031

T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.33

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.027, 0.037

.;.;B;B

Vest4

0.082

MVP

0.14

MPC

0.0053

ClinPred

0.0031

GERP RS

0.099

Varity_R

0.022

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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