19-43015190-C-T

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002785.3(PSG11):​c.890G>A​(p.Gly297Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G297V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PSG11 NM_002785.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSG11	NM_002785.3	c.890G>A	p.Gly297Glu	missense_variant	Exon 4 of 6	ENST00000320078.12	NP_002776.3
PSG11	NM_001113410.2	c.524G>A	p.Gly175Glu	missense_variant	Exon 3 of 5		NP_001106881.1
PSG11	NM_203287.2	c.524G>A	p.Gly175Glu	missense_variant	Exon 3 of 5		NP_976032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSG11	ENST00000320078.12	c.890G>A	p.Gly297Glu	missense_variant	Exon 4 of 6	2	NM_002785.3	ENSP00000319140.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459074 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725908

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	.;T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Uncertain	0.96	.;D;D;D
M_CAP	Benign	0.0014	T
MetaRNN	Pathogenic	0.94	D;D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.7	.;H;.;.
PROVEAN	Pathogenic	-7.2	D;D;D;.
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.28
MutPred		0.93		.;Gain of solvent accessibility (P = 0.0411);.;Gain of solvent accessibility (P = 0.0411);
MVP		0.88
ClinPred		0.90	D
GERP RS		0.98
Varity_R		0.80
gMVP		0.48

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

Other links and lift over

dbSNP: rs754262781; hg19: chr19-43519342;