Variant chr19-42925965-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002783.3(PSG7):c.1051T>G(p.Tyr351Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,612,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PSG7
NM_002783.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.541

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043475688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG7	NM_002783.3 linkuse as main transcript	c.1051T>G	p.Tyr351Asp	missense_variant	5/6	ENST00000406070.7	NP_002774.2	Q13046
PSG7	NM_001206650.2 linkuse as main transcript	c.685T>G	p.Tyr229Asp	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.1051T>G	p.Tyr351Asp	missense_variant	5/6	1	NM_002783.3	ENSP00000421986.1	Q13046
PSG7	ENST00000623675.3 linkuse as main transcript	c.685T>G	p.Tyr229Asp	missense_variant	4/5	1		ENSP00000485117.1	A0A096LNM5
PSG7	ENST00000446844.3 linkuse as main transcript	c.1051T>G	p.Tyr351Asp	missense_variant	5/5	5		ENSP00000470856.1	A0A087WT09
PSG7	ENST00000599226.2 linkuse as main transcript	n.1613T>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

251154

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000545

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1460496

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726528

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151644

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000989

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

Jan 10, 2023

The c.1051T>G (p.Y351D) alteration is located in exon 5 (coding exon 5) of the PSG7 gene. This alteration results from a T to G substitution at nucleotide position 1051, causing the tyrosine (Y) at amino acid position 351 to be replaced by an aspartic acid (D). 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

0.068

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.16

CADD

Benign

0.78

DANN

Benign

0.29

DEOGEN2

Benign

0.017

T;.;.

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.036

T;T;T

MetaRNN

Benign

0.043

T;T;T

PrimateAI

Benign

0.44

Sift4G

Benign

0.63

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.18

MVP

0.10

GERP RS

0.070

Varity_R

0.082

gMVP

0.053

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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