19-42729281-G-T

Position:

chr19-42729281-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021016.4(PSG3):c.1085C>A(p.Ala362Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PSG3
NM_021016.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

PSG3 (HGNC:9520): (pregnancy specific beta-1-glycoprotein 3) The human pregnancy-specific glycoproteins (PSGs) are a family of proteins that are synthesized in large amounts by placental trophoblasts and released into the maternal circulation during pregnancy. Molecular cloning and analysis of several PSG genes has indicated that the PSGs form a subgroup of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin superfamily of genes. Members of the CEA family consist of a single N domain, with structural similarity to the immunoglobulin variable domains, followed by a variable number of immunoglobulin constant-like A and/or B domains. Most PSGs have an arg-gly-asp (RGD) motif, which has been shown to function as an adhesion recognition signal for several integrins, in the N-terminal domain (summary by Teglund et al., 1994 [PubMed 7851896]). For additional general information about the PSG gene family, see PSG1 (MIM 176390).[supplied by OMIM, Oct 2009]

PSG3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12273872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG3	NM_021016.4 linkuse as main transcript	c.1085C>A	p.Ala362Glu	missense_variant	5/7	ENST00000327495.10	NP_066296.2	Q16557
PSG3	XM_011527126.3 linkuse as main transcript	c.872C>A	p.Ala291Glu	missense_variant	4/6		XP_011525428.1
PSG3	XM_011527127.3 linkuse as main transcript	c.775+3503C>A		intron_variant			XP_011525429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PSG3	ENST00000327495.10 linkuse as main transcript	c.1085C>A	p.Ala362Glu	missense_variant	5/7	1	NM_021016.4	ENSP00000332215.5	Q16557
PSG3	ENST00000614582.1 linkuse as main transcript	c.1085C>A	p.Ala362Glu	missense_variant	5/6	1		ENSP00000480223.1	Q16557
PSG3	ENST00000594378.1 linkuse as main transcript	n.*840-65C>A		intron_variant		1		ENSP00000469292.1	M0QXP2
PSG3	ENST00000595140.5 linkuse as main transcript	c.1085C>A	p.Ala362Glu	missense_variant	5/6	5		ENSP00000468936.1	M0QX68

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251408

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.000815

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 12, 2023

The c.1085C>A (p.A362E) alteration is located in exon 5 (coding exon 5) of the PSG3 gene. This alteration results from a C to A substitution at nucleotide position 1085, causing the alanine (A) at amino acid position 362 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

3.1

M;.;M

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.6

D;.;.

REVEL

Benign

0.082

Sift

Uncertain

0.021

D;.;.

Sift4G

Uncertain

0.014

D;D;D

Polyphen

0.78

P;.;P

Vest4

0.37

MutPred

0.62

Gain of disorder (P = 0.0227);Gain of disorder (P = 0.0227);Gain of disorder (P = 0.0227);

MVP

0.67

MPC

0.0054

ClinPred

0.38

GERP RS

-0.99

Varity_R

0.28

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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