Genetic Variant PSG11:p.Ala263Thr (chr19-43015293-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002785.3(PSG11):c.787G>A(p.Ala263Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,610,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A263S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

PSG11
NM_002785.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.106

Publications

7 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07248506).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002785.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSG11	NM_002785.3	MANE Select	c.787G>A	p.Ala263Thr	missense	Exon 4 of 6	NP_002776.3
PSG11	NM_001113410.2		c.421G>A	p.Ala141Thr	missense	Exon 3 of 5	NP_001106881.1	Q9UQ72-2
PSG11	NM_203287.2		c.421G>A	p.Ala141Thr	missense	Exon 3 of 5	NP_976032.2	Q9UQ72-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSG11	ENST00000320078.12	TSL:2 MANE Select	c.787G>A	p.Ala263Thr	missense	Exon 4 of 6	ENSP00000319140.7	Q9UQ72-1
PSG11	ENST00000306322.7	TSL:1	c.421G>A	p.Ala141Thr	missense	Exon 3 of 5	ENSP00000304913.6	Q9UQ72-2
PSG11	ENST00000598133.2	TSL:5	c.787G>A	p.Ala263Thr	missense	Exon 4 of 5	ENSP00000472372.2	M0R276

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151368

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000419

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000478

AC:

AN:

251204

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1458948

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

725878

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33296

American (AMR)

AF:

0.0000671

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39638

South Asian (SAS)

AF:

0.000174

AC:

AN:

86024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1109730

Other (OTH)

AF:

0.0000332

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000396

AC:

AN:

151484

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74034

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41172

American (AMR)

AF:

0.00

AC:

AN:

15166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000419

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67882

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.0092

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.66

M_CAP

Benign

0.00047

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

PhyloP100

-0.11

PROVEAN

Benign

-1.8

REVEL

Benign

0.023

Sift

Benign

0.47

Sift4G

Benign

0.39

Polyphen

0.0090

Vest4

0.11

MutPred

0.48

Loss of stability (P = 0.2032)

MVP

0.11

ClinPred

0.012

GERP RS

-0.046

Varity_R

0.058

gMVP

0.081

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over