Variant 19-43018852-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002785.3(PSG11):c.627G>T(p.Lys209Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,612,010 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 3 hom. )

Consequence

PSG11
NM_002785.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0120

Variant links:

Genes affected

PSG11 (HGNC:9516): (pregnancy specific beta-1-glycoprotein 11) The human pregnancy-specific glycoproteins (PSGs) are a group of molecules that are mainly produced by the placental syncytiotrophoblasts during pregnancy. PSGs comprise a subgroup of the carcinoembryonic antigen (CEA) family, which belongs to the immunoglobulin superfamily. For additional general information about the PSG gene family, see PSG1 (MIM 176390).[supplied by OMIM, Oct 2009]

PSG11 links:

PSG11-AS1 (HGNC:56358): (PSG11, PSG2 and PSG5 antisense RNA 1)

PSG11-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052987367).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PSG11	NM_002785.3 linkuse as main transcript	c.627G>T	p.Lys209Asn	missense_variant	3/6	ENST00000320078.12	NP_002776.3
PSG11	NM_001113410.2 linkuse as main transcript	c.261G>T	p.Lys87Asn	missense_variant	2/5		NP_001106881.1
PSG11	NM_203287.2 linkuse as main transcript	c.261G>T	p.Lys87Asn	missense_variant	2/5		NP_976032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSG11	ENST00000320078.12 linkuse as main transcript	c.627G>T	p.Lys209Asn	missense_variant	3/6	2	NM_002785.3	ENSP00000319140	P2	Q9UQ72-1
PSG11-AS1	ENST00000635495.1 linkuse as main transcript	n.182+41208C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151428

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

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:

0.0000597

AC:

AN:

251052

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1460582

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726572

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.000881

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151428

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73934

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Dec 26, 2023

The c.627G>T (p.K209N) alteration is located in exon 3 (coding exon 3) of the PSG11 gene. This alteration results from a G to T substitution at nucleotide position 627, causing the lysine (K) at amino acid position 209 to be replaced by an asparagine (N). 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

0.25

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.9

DANN

Benign

0.95

DEOGEN2

Benign

0.042

.;T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.14

.;T;T

M_CAP

Benign

0.00078

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L;.

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Uncertain

-2.8

D;N;D

REVEL

Benign

0.021

Sift

Uncertain

0.014

D;D;D

Sift4G

Benign

0.061

T;D;T

Polyphen

0.63

P;B;P

Vest4

0.23

MutPred

0.62

.;Loss of ubiquitination at K209 (P = 0.0192);.;

MVP

0.31

ClinPred

0.12

GERP RS

-0.015

Varity_R

0.12

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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