Variant 19-42868762-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_001184825.2(PSG1):c.982G>A(p.Val328Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000565 in 1,611,976 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 2 hom. )

Consequence

PSG1
NM_001184825.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0430

Variant links:

Genes affected

PSG1 (HGNC:9514): (pregnancy specific beta-1-glycoprotein 1) The human placenta is a multihormonal endocrine organ that produces hormones, enzymes, and other molecules that support fetal survival and development. Pregnancy-specific beta-1-glycoprotein (PSBG, PSG) is a major product of the syncytiotrophoblast, reaching concentrations of 100 to 290 mg/l at term in the serum of pregnant women (Horne et al., 1976 [PubMed 971765]). PSG is a member of the immunoglobulin (Ig) superfamily (Watanabe and Chou, 1988 [PubMed 3257488]; Streydio et al., 1988 [PubMed 3260773]).[supplied by OMIM, Oct 2009]

PSG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04452905).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG1	NM_001184825.2 link	c.982G>A	p.Val328Ile	missense_variant	4/6	ENST00000436291.7	NP_001171754.1	P11464-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSG1	ENST00000436291.7 link	c.982G>A	p.Val328Ile	missense_variant	4/6	1	NM_001184825.2	ENSP00000413041.2		P11464-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151478

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00106

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

225780

Hom.:

AF XY:

0.00000831

AC XY:

AN XY:

120390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000332

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000542

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1460380

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000796

GnomAD4 genome

AF:

0.000211

AC:

AN:

151596

Hom.:

Cov.:

AF XY:

0.0000675

AC XY:

AN XY:

74056

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000583

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.0000869

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000826

AC:

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 26, 2024

The c.982G>A (p.V328I) alteration is located in exon 4 (coding exon 4) of the PSG1 gene. This alteration results from a G to A substitution at nucleotide position 982, causing the valine (V) at amino acid position 328 to be replaced by an isoleucine (I). 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

0.096

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.0

DANN

Benign

0.93

DEOGEN2

Benign

0.0026

T;T;.;T;.;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.76

T;T;T;T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.045

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;L;.;L;L

PROVEAN

Benign

-0.69

N;.;.;N;N;N

REVEL

Benign

0.046

Sift

Benign

0.19

T;.;.;T;T;T

Sift4G

Uncertain

0.034

D;T;D;T;D;D

Polyphen

0.93

P;.;B;B;P;P

Vest4

0.099

MutPred

0.56

Loss of phosphorylation at T325 (P = 0.1497);.;Loss of phosphorylation at T325 (P = 0.1497);.;Loss of phosphorylation at T325 (P = 0.1497);Loss of phosphorylation at T325 (P = 0.1497);

MVP

0.040

MPC

0.019

ClinPred

0.069

GERP RS

0.69

Varity_R

0.071

gMVP

0.048

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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