chr19-43018892-G-C

Variant names:

• chr19-43018892-G-C
• rs200217396
• NM_002785.3:c.587C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002785.3(PSG11):​c.587C>G​(p.Ser196Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000072 in 1,611,976 control chromosomes in the GnomAD database, including 5 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 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (5 hom.)
• Consequence: PSG11 NM_002785.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.205
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1891526).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

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.587C>G	p.Ser196Cys	missense	Exon 3 of 6	NP_002776.3
	PSG11	NM_001113410.2		c.221C>G	p.Ser74Cys	missense	Exon 2 of 5	NP_001106881.1	Q9UQ72-2
	PSG11	NM_203287.2		c.221C>G	p.Ser74Cys	missense	Exon 2 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.587C>G	p.Ser196Cys	missense	Exon 3 of 6	ENSP00000319140.7	Q9UQ72-1
	PSG11	ENST00000306322.7	TSL:1	c.221C>G	p.Ser74Cys	missense	Exon 2 of 5	ENSP00000304913.6	Q9UQ72-2
	PSG11	ENST00000403486.5	TSL:2	c.221C>G	p.Ser74Cys	missense	Exon 2 of 5	ENSP00000385427.1	Q9UQ72-2

Frequencies

GnomAD3 genomes AF: 0.0000661 AC: 10 AN: 151372 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000916 AC: 23 AN: 251126 AF XY: 0.000103

Gnomad AFR exome AF: 0.000123

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: 0.000141

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000726 AC: 106 AN: 1460604 Hom.: 5 Cov.: 34 AF XY: 0.0000716 AC XY: 52 AN XY: 726584

African (AFR) AF: 0.0000300 AC: 1 AN: 33382

American (AMR) AF: 0.0000671 AC: 3 AN: 44694

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.0000657 AC: 73 AN: 1111194

Other (OTH) AF: 0.000182 AC: 11 AN: 60326

GnomAD4 genome AF: 0.0000661 AC: 10 AN: 151372 Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 4 AN XY: 73906

African (AFR) AF: 0.0000244 AC: 1 AN: 41036

American (AMR) AF: 0.0000659 AC: 1 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67890

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000248 Hom.: 1

Bravo AF: 0.0000869

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3468

EpiCase AF: 0.0000546

EpiControl AF: 0.000178

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	0.34
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.00046	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.20
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.032
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.19
MVP		0.22
ClinPred		0.53	D
GERP RS		-0.57
Varity_R		0.29
gMVP		0.12
Mutation Taster		=98/2	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: rs200217396; hg19: chr19-43523044;