Variant 19-42868115-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001184825.2(PSG1):c.1229C>G(p.Thr410Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,280 control chromosomes in the GnomAD database, including 1 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 1 hom. )

Consequence

PSG1
NM_001184825.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.70

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062149614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG1	NM_001184825.2 link	c.1229C>G	p.Thr410Arg	missense_variant	5/6	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.1229C>G	p.Thr410Arg	missense_variant	5/6	1	NM_001184825.2	ENSP00000413041.2		P11464-1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151570

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:

0.000194

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:

0.00000797

AC:

AN:

250966

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.00000411

AC:

AN:

1460710

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151570

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73974

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

Jul 27, 2024

The c.1229C>G (p.T410R) alteration is located in exon 5 (coding exon 5) of the PSG1 gene. This alteration results from a C to G substitution at nucleotide position 1229, causing the threonine (T) at amino acid position 410 to be replaced by an arginine (R). 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

0.065

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.0070

DANN

Benign

0.55

DEOGEN2

Benign

0.0053

T;T;.;T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.65

T;T;T;T;T;T

M_CAP

Benign

0.00051

MetaRNN

Benign

0.062

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.89

L;.;L;.;L;L

PROVEAN

Benign

-1.4

N;.;.;N;N;N

REVEL

Benign

0.050

Sift

Benign

0.14

T;.;.;D;T;T

Sift4G

Benign

0.095

T;T;T;T;T;T

Polyphen

0.0060

B;.;B;B;.;B

Vest4

0.16

MutPred

0.27

Gain of MoRF binding (P = 0.012);.;Gain of MoRF binding (P = 0.012);.;Gain of MoRF binding (P = 0.012);Gain of MoRF binding (P = 0.012);

MVP

0.030

MPC

0.0087

ClinPred

0.056

GERP RS

-3.2

Varity_R

0.085

gMVP

0.046

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