19-42729838-A-T

Variant names:

• chr19-42729838-A-T
• rs1422651867
• NM_021016.4:c.928T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021016.4(PSG3):​c.928T>A​(p.Cys310Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PSG3 NM_021016.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSG3	NM_021016.4	c.928T>A	p.Cys310Ser	missense_variant	Exon 4 of 7	ENST00000327495.10	NP_066296.2
PSG3	XM_011527126.3	c.776-461T>A		intron_variant	Intron 3 of 5		XP_011525428.1
PSG3	XM_011527127.3	c.775+2946T>A		intron_variant	Intron 3 of 4		XP_011525429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSG3	ENST00000327495.10	c.928T>A	p.Cys310Ser	missense_variant	Exon 4 of 7	1	NM_021016.4	ENSP00000332215.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461304 Hom.: 0 Cov.: 38 AF XY: 0.00000413 AC XY: 3 AN XY: 726952

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.30	T;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.015	N
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Benign	0.0018	T
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.9	D;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D;.;.
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.53
MutPred		0.74		Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);
MVP		0.68
MPC		0.010
ClinPred		0.72	D
GERP RS		1.1
Varity_R		0.35
gMVP		0.48

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: rs1422651867; hg19: chr19-43233990;