19-42729375-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021016.4(PSG3):c.991G>A(p.Gly331Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,458,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PSG3
NM_021016.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.769

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSG3	NM_021016.4 link	c.991G>A	p.Gly331Ser	missense_variant, splice_region_variant	Exon 5 of 7	ENST00000327495.10	NP_066296.2	Q16557
PSG3	XM_011527126.3 link	c.778G>A	p.Gly260Ser	missense_variant, splice_region_variant	Exon 4 of 6		XP_011525428.1
PSG3	XM_011527127.3 link	c.775+3409G>A		intron_variant	Intron 3 of 4		XP_011525429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PSG3	ENST00000327495.10 link	c.991G>A	p.Gly331Ser	missense_variant, splice_region_variant	Exon 5 of 7	1	NM_021016.4	ENSP00000332215.5	Q16557
PSG3	ENST00000614582.1 link	c.991G>A	p.Gly331Ser	missense_variant, splice_region_variant	Exon 5 of 6	1		ENSP00000480223.1	Q16557
PSG3	ENST00000594378.1 link	n.*840-159G>A		intron_variant	Intron 5 of 7	1		ENSP00000469292.1	M0QXP2
PSG3	ENST00000595140.5 link	c.991G>A	p.Gly331Ser	missense_variant, splice_region_variant	Exon 5 of 6	5		ENSP00000468936.1	M0QX68

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

247938

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000110

AC:

AN:

1458740

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.991G>A (p.G331S) alteration is located in exon 5 (coding exon 5) of the PSG3 gene. This alteration results from a G to A substitution at nucleotide position 991, causing the glycine (G) at amino acid position 331 to be replaced by a serine (S). 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

0.28

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.041

T;T;T

Eigen

Benign

-0.086

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.21

LIST_S2

Pathogenic

0.98

.;D;D

M_CAP

Benign

0.00068

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.7

M;.;M

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-4.9

D;.;.

REVEL

Benign

0.069

Sift

Benign

0.19

T;.;.

Sift4G

Uncertain

0.011

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.28

MutPred

0.45

Loss of catalytic residue at G331 (P = 0.281);Loss of catalytic residue at G331 (P = 0.281);Loss of catalytic residue at G331 (P = 0.281);

MVP

0.44

MPC

0.012

ClinPred

0.66

GERP RS

1.4

Varity_R

0.16

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.27

Position offset: 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