19-42729167-G-A

Variant names:

• chr19-42729167-G-A
• NM_021016.4:c.1199C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_021016.4(PSG3):​c.1199C>T​(p.Ala400Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSG3 NM_021016.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.824

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053198814).
• BP6: Variant 19-42729167-G-A is Benign according to our data. Variant chr19-42729167-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2553543.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSG3	NM_021016.4	c.1199C>T	p.Ala400Val	missense_variant	Exon 5 of 7	ENST00000327495.10	NP_066296.2
PSG3	XM_011527126.3	c.986C>T	p.Ala329Val	missense_variant	Exon 4 of 6		XP_011525428.1
PSG3	XM_011527127.3	c.775+3617C>T		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.1199C>T	p.Ala400Val	missense_variant	Exon 5 of 7	1	NM_021016.4	ENSP00000332215.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 31, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.27
DANN	Benign	0.48
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00097	N
LIST_S2	Benign	0.84	.;T;T
M_CAP	Benign	0.00069	T
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.80	N;.;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.9	N;.;.
REVEL	Benign	0.050
Sift	Benign	0.51	T;.;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.97	D;.;D
Vest4		0.043
MutPred		0.19		Loss of disorder (P = 0.1023);Loss of disorder (P = 0.1023);Loss of disorder (P = 0.1023);
MVP		0.11
MPC		0.0038
ClinPred		0.12	T
GERP RS		-1.8
Varity_R		0.026
gMVP		0.019

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-43233319;