19-43015250-C-G

Variant names:

• chr19-43015250-C-G
• rs745354526
• NM_002785.3:c.830G>C

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.830G>C​(p.Gly277Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,611,402 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (2 hom.)
• Consequence: PSG11 NM_002785.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.253
• 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=0.19467157).
• BS2: High Homozygotes in GnomAdExome4 at 2 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.830G>C	p.Gly277Ala	missense	Exon 4 of 6	NP_002776.3
	PSG11	NM_001113410.2		c.464G>C	p.Gly155Ala	missense	Exon 3 of 5	NP_001106881.1	Q9UQ72-2
	PSG11	NM_203287.2		c.464G>C	p.Gly155Ala	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.830G>C	p.Gly277Ala	missense	Exon 4 of 6	ENSP00000319140.7	Q9UQ72-1
	PSG11	ENST00000306322.7	TSL:1	c.464G>C	p.Gly155Ala	missense	Exon 3 of 5	ENSP00000304913.6	Q9UQ72-2
	PSG11	ENST00000598133.2	TSL:5	c.830G>C	p.Gly277Ala	missense	Exon 4 of 5	ENSP00000472372.2	M0R276

Frequencies

GnomAD3 genomes AF: 0.000218 AC: 33 AN: 151402 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000780

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251254 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0000289

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: 0.0000103 AC: 15 AN: 1460000 Hom.: 2 Cov.: 77 AF XY: 0.00000275 AC XY: 2 AN XY: 726354

African (AFR) AF: 0.000390 AC: 13 AN: 33354

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 86050

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

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110662

Other (OTH) AF: 0.0000332 AC: 2 AN: 60308

GnomAD4 genome AF: 0.000218 AC: 33 AN: 151402 Hom.: 1 Cov.: 33 AF XY: 0.000257 AC XY: 19 AN XY: 73930

African (AFR) AF: 0.000780 AC: 32 AN: 41028

American (AMR) AF: 0.0000659 AC: 1 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67882

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000181

ExAC AF: 0.0000330 AC: 4

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	Uncertain	0.50
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.25
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.26
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.95	P
Vest4		0.24
MVP		0.76
ClinPred		0.32	T
GERP RS		-1.1
Varity_R		0.36
gMVP		0.087
Mutation Taster		=100/0	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: rs745354526; hg19: chr19-43519402;