Genetic Variant PSG3:n.*56A>C (chr19-42733612-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000594378.1(PSG3):n.*56A>C variant causes a non coding transcript exon 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
ENST00000594378.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.970

Publications

2 publications found

Variant links:

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 links:

LIPE-AS1 (HGNC:48589): (LIPE antisense RNA 1)

LIPE-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
PSG3	NM_021016.4 link	c.431-550A>C	intron_variant	Intron 2 of 6	ENST00000327495.10	NP_066296.2	Q16557
PSG3	XM_011527126.3 link	c.497-550A>C	intron_variant	Intron 2 of 5		XP_011525428.1
PSG3	XM_011527127.3 link	c.497-550A>C	intron_variant	Intron 2 of 4		XP_011525429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSG3	ENST00000327495.10 link	c.431-550A>C		intron_variant	Intron 2 of 6	1	NM_021016.4	ENSP00000332215.5		Q16557

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

95628

AN:

151170

Hom.:

31664

Cov.:

show subpopulations

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.:

AF XY:

0.535

AC XY:

1716

AN XY:

3208

show subpopulations

African (AFR)

AF:

0.808

AC:

AN:

American (AMR)

AF:

0.609

AC:

1087

AN:

1786

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.398

AC:

AN:

216

South Asian (SAS)

AF:

0.573

AC:

379

AN:

662

European-Finnish (FIN)

AF:

0.400

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.509

AC:

1632

AN:

3204

Other (OTH)

AF:

0.472

AC:

103

AN:

218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

139

209

278

348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.633

AC:

95750

AN:

151290

Hom.:

31722

Cov.:

AF XY:

0.631

AC XY:

46663

AN XY:

73908

show subpopulations

African (AFR)

AF:

0.840

AC:

34439

AN:

40990

American (AMR)

AF:

0.608

AC:

9241

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

1892

AN:

3466

East Asian (EAS)

AF:

0.449

AC:

2306

AN:

5138

South Asian (SAS)

AF:

0.604

AC:

2898

AN:

4796

European-Finnish (FIN)

AF:

0.592

AC:

6225

AN:

10512

Middle Eastern (MID)

AF:

0.616

AC:

180

AN:

292

European-Non Finnish (NFE)

AF:

0.545

AC:

36989

AN:

67876

Other (OTH)

AF:

0.586

AC:

1232

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1538

3075

4613

6150

7688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.49

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over