Variant 19-43015244-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002785.3(PSG11):c.836T>C(p.Phe279Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,036 control chromosomes in the GnomAD database, including 1 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: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 1 hom. )

Consequence

PSG11
NM_002785.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.676

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 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=0.09548509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG11	NM_002785.3 link	c.836T>C	p.Phe279Ser	missense_variant	4/6	ENST00000320078.12	NP_002776.3	Q9UQ72-1
PSG11	NM_001113410.2 link	c.470T>C	p.Phe157Ser	missense_variant	3/5		NP_001106881.1	Q9UQ72-2
PSG11	NM_203287.2 link	c.470T>C	p.Phe157Ser	missense_variant	3/5		NP_976032.2	Q9UQ72-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSG11	ENST00000320078.12 link	c.836T>C	p.Phe279Ser	missense_variant	4/6	2	NM_002785.3	ENSP00000319140.7		Q9UQ72-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251256

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135778

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:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460036

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726358

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000140

Hom.:

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

Oct 01, 2024

The c.836T>C (p.F279S) alteration is located in exon 4 (coding exon 4) of the PSG11 gene. This alteration results from a T to C substitution at nucleotide position 836, causing the phenylalanine (F) at amino acid position 279 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

0.32

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.4

DANN

Benign

0.35

DEOGEN2

Benign

0.021

.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00094

LIST_S2

Benign

0.66

.;T;T;T

M_CAP

Benign

0.00091

MetaRNN

Benign

0.095

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.35

.;N;.;.

PROVEAN

Pathogenic

-6.1

D;D;D;.

REVEL

Benign

0.012

Sift

Benign

0.055

T;T;T;.

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.30

B;B;B;.

Vest4

0.062

MutPred

0.51

.;Gain of disorder (P = 0.0031);.;Gain of disorder (P = 0.0031);

MVP

0.055

ClinPred

0.18

GERP RS

-1.9

Varity_R

0.15

gMVP

0.12

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.

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