19-43015293-C-A

Variant names:

• chr19-43015293-C-A
• rs527275238
• NM_002785.3:c.787G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.106
• Publications: 7 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSG11	NM_002785.3	MANE Select	c.787G>T	p.Ala263Ser	missense	Exon 4 of 6	NP_002776.3
	PSG11	NM_001113410.2		c.421G>T	p.Ala141Ser	missense	Exon 3 of 5	NP_001106881.1	Q9UQ72-2
	PSG11	NM_203287.2		c.421G>T	p.Ala141Ser	missense	Exon 3 of 5	NP_976032.2	Q9UQ72-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSG11	ENST00000320078.12	TSL:2 MANE Select	c.787G>T	p.Ala263Ser	missense	Exon 4 of 6	ENSP00000319140.7	Q9UQ72-1
	PSG11	ENST00000306322.7	TSL:1	c.421G>T	p.Ala141Ser	missense	Exon 3 of 5	ENSP00000304913.6	Q9UQ72-2
	PSG11	ENST00000598133.2	TSL:5	c.787G>T	p.Ala263Ser	missense	Exon 4 of 5	ENSP00000472372.2	M0R276

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151368 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251204 AF XY: 0.0000368

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 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

African (AFR) AF: 0.0000300 AC: 1 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1109730

Other (OTH) AF: 0.0000166 AC: 1 AN: 60280

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151368 Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2 AN XY: 73908

African (AFR) AF: 0.0000244 AC: 1 AN: 41052

American (AMR) AF: 0.00 AC: 0 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4776

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67890

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.00073	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.11
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.032
Sift	Benign	0.044	D
Sift4G	Benign	0.13	T
Polyphen		0.012	B
Vest4		0.19
MutPred		0.66		Gain of disorder (P = 0.0303)
MVP		0.14
ClinPred		0.050	T
GERP RS		-0.046
Varity_R		0.12
gMVP		0.096
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs527275238; hg19: chr19-43519445;