rs8103264

chr19-42736227-C-Gchr19-42736227-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021016.4(PSG3):c.430+2497G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,086 control chromosomes in the GnomAD database, including 3,729 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (3729 hom., cov: 32)
• Consequence: PSG3 NM_021016.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSG3	NM_021016.4	c.430+2497G>C		intron_variant		ENST00000327495.10
PSG3	XM_011527126.3	c.496+2497G>C		intron_variant
PSG3	XM_011527127.3	c.496+2497G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSG3	ENST00000327495.10	c.430+2497G>C		intron_variant		1	NM_021016.4	P2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25319 AN: 151968 Hom.: 3698 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0903

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.167 AC: 25406 AN: 152086 Hom.: 3729 Cov.: 32 AF XY: 0.163 AC XY: 12147 AN XY: 74364

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0903

Gnomad4 EAS AF: 0.0270

Gnomad4 SAS AF: 0.0998

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.145

Alfa AF: 0.130 Hom.: 301

Bravo AF: 0.182

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.0
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs8103264; hg19: chr19-43240379;