19-43015169-C-G

Variant names:

• chr19-43015169-C-G
• rs770296835
• NM_002785.3:c.911G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002785.3(PSG11):​c.911G>C​(p.Arg304Pro) 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 1,460,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. R304H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PSG11 NM_002785.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33994907).

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.911G>C	p.Arg304Pro	missense	Exon 4 of 6	NP_002776.3
	PSG11	NM_001113410.2		c.545G>C	p.Arg182Pro	missense	Exon 3 of 5	NP_001106881.1	Q9UQ72-2
	PSG11	NM_203287.2		c.545G>C	p.Arg182Pro	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.911G>C	p.Arg304Pro	missense	Exon 4 of 6	ENSP00000319140.7	Q9UQ72-1
	PSG11	ENST00000306322.7	TSL:1	c.545G>C	p.Arg182Pro	missense	Exon 3 of 5	ENSP00000304913.6	Q9UQ72-2
	PSG11	ENST00000598133.2	TSL:5	c.911G>C	p.Arg304Pro	missense	Exon 4 of 5	ENSP00000472372.2	M0R276

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460212 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726420

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44692

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86052

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

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110866

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.00086	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		-0.42
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.12
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.48		Loss of catalytic residue at R304 (P = 0.0194)
MVP		0.22
ClinPred		0.67	D
GERP RS		-1.9
Varity_R		0.60
gMVP		0.40
Mutation Taster		=96/4	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: rs770296835; hg19: chr19-43519321;