NM_002785.3:c.890G>T

Variant names:

• chr19-43015190-C-A
• rs754262781
• NM_002785.3:c.890G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002785.3(PSG11):​c.890G>T​(p.Gly297Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,610,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G297E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: PSG11 NM_002785.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83
• 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

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.890G>T	p.Gly297Val	missense	Exon 4 of 6	NP_002776.3
	PSG11	NM_001113410.2		c.524G>T	p.Gly175Val	missense	Exon 3 of 5	NP_001106881.1	Q9UQ72-2
	PSG11	NM_203287.2		c.524G>T	p.Gly175Val	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.890G>T	p.Gly297Val	missense	Exon 4 of 6	ENSP00000319140.7	Q9UQ72-1
	PSG11	ENST00000306322.7	TSL:1	c.524G>T	p.Gly175Val	missense	Exon 3 of 5	ENSP00000304913.6	Q9UQ72-2
	PSG11	ENST00000598133.2	TSL:5	c.890G>T	p.Gly297Val	missense	Exon 4 of 5	ENSP00000472372.2	M0R276

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151428 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000122

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251218 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000617 AC: 9 AN: 1459074 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 725908

African (AFR) AF: 0.0000300 AC: 1 AN: 33328

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000721 AC: 8 AN: 1109852

Other (OTH) AF: 0.00 AC: 0 AN: 60270

GnomAD4 genome AF: 0.0000396 AC: 6 AN: 151428 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 73944

African (AFR) AF: 0.000122 AC: 5 AN: 41046

American (AMR) AF: 0.00 AC: 0 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67904

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0015	T
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	-0.0033	T
MutationAssessor	Pathogenic	4.4	H
PhyloP100		1.8
PROVEAN	Pathogenic	-8.2	D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.94		Loss of disorder (P = 0.1084)
MVP		0.90
ClinPred		1.0	D
GERP RS		0.98
Varity_R		0.60
gMVP		0.42
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: rs754262781; hg19: chr19-43519342;