Variant chr19-42906951-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001031850.4(PSG6):c.1211T>G(p.Ile404Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 1,612,242 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0038 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 164 hom. )

Consequence

PSG6
NM_001031850.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.963

Variant links:

Genes affected

PSG6 (HGNC:9523): (pregnancy specific beta-1-glycoprotein 6) 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. The protein encoded by this gene contains the Arg-Gly-Asp tripeptide associated with cellular adhesion and recognition. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

PSG6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033855736).

BP6

Variant 19-42906951-A-C is Benign according to our data. Variant chr19-42906951-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650048.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSG6	NM_001031850.4 linkuse as main transcript	c.1211T>G	p.Ile404Ser	missense_variant	5/6	ENST00000187910.7
PSG6	NM_002782.5 linkuse as main transcript	c.1211T>G	p.Ile404Ser	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSG6	ENST00000187910.7 linkuse as main transcript	c.1211T>G	p.Ile404Ser	missense_variant	5/6	1	NM_001031850.4	A2	Q00889-2

Frequencies

GnomAD3 genomes

AF:

0.00380

AC:

576

AN:

151432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000753

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00132

Gnomad ASJ

AF:

0.00492

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00209

Gnomad FIN

AF:

0.00834

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00595

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00431

AC:

1082

AN:

250988

Hom.:

AF XY:

0.00443

AC XY:

601

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00301

Gnomad FIN exome

AF:

0.00855

Gnomad NFE exome

AF:

0.00618

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00402

AC:

5874

AN:

1460692

Hom.:

164

Cov.:

AF XY:

0.00415

AC XY:

3013

AN XY:

726636

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00329

Gnomad4 FIN exome

AF:

0.00929

Gnomad4 NFE exome

AF:

0.00427

Gnomad4 OTH exome

AF:

0.00330

GnomAD4 genome

AF:

0.00381

AC:

578

AN:

151550

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

277

AN XY:

74060

show subpopulations

Gnomad4 AFR

AF:

0.000775

Gnomad4 AMR

AF:

0.00132

Gnomad4 ASJ

AF:

0.00492

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00231

Gnomad4 FIN

AF:

0.00834

Gnomad4 NFE

AF:

0.00595

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00569

Hom.:

Bravo

AF:

0.00279

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00448

AC:

544

EpiCase

AF:

0.00486

EpiControl

AF:

0.00474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

PSG6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.021

DANN

Benign

0.17

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.000060

LIST_S2

Benign

0.055

T;T;T

M_CAP

Benign

0.00047

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.3

N;.;N

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

2.0

N;N;N

REVEL

Benign

0.024

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.79

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.091

MVP

0.014

ClinPred

0.0012

GERP RS

0.39

Varity_R

0.039

gMVP

0.032

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