Variant chr19-42925890-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002783.3(PSG7):c.1126G>A(p.Gly376Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000596 in 1,612,046 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 3 hom. )

Consequence

PSG7
NM_002783.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.706

Variant links:

Genes affected

PSG7 (HGNC:9524): (pregnancy specific beta-1-glycoprotein 7) This gene is a member of the pregnancy-specific glycoprotein (PSG) gene family. The PSG genes are a subgroup of the carcinoembryonic antigen (CEA) family of immunoglobulin-like genes, and are found in a gene cluster at 19q13.1-q13.2 telomeric to another cluster of CEA-related genes. The PSG genes are expressed by placental trophoblasts and released into the maternal circulation during pregnancy, and are thought to be essential for maintenance of normal pregnancy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

PSG7 links:

PSG7 (HGNC:):

PSG7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09681207).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG7	NM_002783.3 linkuse as main transcript	c.1126G>A	p.Gly376Arg	missense_variant	5/6	ENST00000406070.7	NP_002774.2	Q13046
PSG7	NM_001206650.2 linkuse as main transcript	c.760G>A	p.Gly254Arg	missense_variant	4/5		NP_001193579.1	A0A096LNM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PSG7	ENST00000406070.7 linkuse as main transcript	c.1126G>A	p.Gly376Arg	missense_variant	5/6	1	NM_002783.3	ENSP00000421986.1	Q13046
PSG7	ENST00000623675.3 linkuse as main transcript	c.760G>A	p.Gly254Arg	missense_variant	4/5	1		ENSP00000485117.1	A0A096LNM5
PSG7	ENST00000446844.3 linkuse as main transcript	c.1126G>A	p.Gly376Arg	missense_variant	5/5	5		ENSP00000470856.1	A0A087WT09
PSG7	ENST00000599226.2 linkuse as main transcript	n.1688G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000528

AC:

AN:

151484

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

251144

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000603

AC:

AN:

1460562

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000738

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000528

AC:

AN:

151484

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

73922

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 08, 2024

The c.1126G>A (p.G376R) alteration is located in exon 5 (coding exon 5) of the PSG7 gene. This alteration results from a G to A substitution at nucleotide position 1126, causing the glycine (G) at amino acid position 376 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;.;.

FATHMM_MKL

Benign

0.00022

LIST_S2

Uncertain

0.97

D;D;D

MetaRNN

Benign

0.097

T;T;T

PrimateAI

Benign

0.39

Sift4G

Uncertain

0.032

D;D;D

Polyphen

0.58

P;.;.

Vest4

0.21

MVP

0.12

GERP RS

0.15

Varity_R

0.047

gMVP

0.052

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over