19-43015293-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002785.3(PSG11):​c.787G>T​(p.Ala263Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,610,316 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.000019 ( 1 hom. )

Consequence

PSG11
NM_002785.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.106
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-AS1 (HGNC:56358): (PSG11, PSG2 and PSG5 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20144957).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSG11NM_002785.3 linkc.787G>T p.Ala263Ser missense_variant 4/6 ENST00000320078.12 NP_002776.3 Q9UQ72-1
PSG11NM_001113410.2 linkc.421G>T p.Ala141Ser missense_variant 3/5 NP_001106881.1 Q9UQ72-2
PSG11NM_203287.2 linkc.421G>T p.Ala141Ser missense_variant 3/5 NP_976032.2 Q9UQ72-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSG11ENST00000320078.12 linkc.787G>T p.Ala263Ser missense_variant 4/62 NM_002785.3 ENSP00000319140.7 Q9UQ72-1

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151368
Hom.:
0
Cov.:
32
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:
0.00
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251204
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135750
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:
0.000185
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1458948
Hom.:
1
Cov.:
34
AF XY:
0.0000207
AC XY:
15
AN XY:
725878
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000131
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151368
Hom.:
0
Cov.:
32
AF XY:
0.0000271
AC XY:
2
AN XY:
73908
show subpopulations
Gnomad4 AFR
AF:
0.0000244
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000412
AC:
5

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 submitterclinical testingAmbry GeneticsDec 17, 2023The c.787G>T (p.A263S) alteration is located in exon 4 (coding exon 4) of the PSG11 gene. This alteration results from a G to T substitution at nucleotide position 787, causing the alanine (A) at amino acid position 263 to be replaced by a serine (S). 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
0.13
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
9.2
DANN
Uncertain
0.98
DEOGEN2
Benign
0.010
.;T;.;.
Eigen
Benign
-0.98
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.72
.;T;T;T
M_CAP
Benign
0.00073
T
MetaRNN
Benign
0.20
T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.1
.;M;.;.
PROVEAN
Benign
-1.7
N;N;N;.
REVEL
Benign
0.032
Sift
Benign
0.044
D;D;D;.
Sift4G
Benign
0.13
T;T;T;T
Polyphen
0.012
B;B;B;.
Vest4
0.19
MutPred
0.66
.;Gain of disorder (P = 0.0303);.;Gain of disorder (P = 0.0303);
MVP
0.14
ClinPred
0.050
T
GERP RS
-0.046
Varity_R
0.12
gMVP
0.096

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

LitVar

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

Other links and lift over

dbSNP: rs527275238; hg19: chr19-43519445; API