19-42733612-T-G

Position:

• chr19-42733612-T-G

Variant summary

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

The NM_021016.4(PSG3):​c.431-550A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 157,474 control chromosomes in the GnomAD database, including 32,683 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 0.63 (31722 hom., cov: 30)
  • Exomes 𝑓: 0.54 (961 hom.)
• Consequence: PSG3 NM_021016.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG3	NM_021016.4	c.431-550A>C		intron_variant		ENST00000327495.10	NP_066296.2
PSG3	XM_011527126.3	c.497-550A>C		intron_variant			XP_011525428.1
PSG3	XM_011527127.3	c.497-550A>C		intron_variant			XP_011525429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSG3	ENST00000327495.10	c.431-550A>C		intron_variant		1	NM_021016.4	ENSP00000332215.5

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95628 AN: 151170 Hom.: 31664 Cov.: 30

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.584

GnomAD4 exome AF: 0.540 AC: 3340 AN: 6184 Hom.: 961 Cov.: 0 AF XY: 0.535 AC XY: 1716 AN XY: 3208

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.398

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.509

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.633 AC: 95750 AN: 151290 Hom.: 31722 Cov.: 30 AF XY: 0.631 AC XY: 46663 AN XY: 73908

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.586

Alfa AF: 0.606 Hom.: 4342

Bravo AF: 0.641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.87
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: rs4030933; hg19: chr19-43237764;