19-43015166-T-C

Variant names:

• chr19-43015166-T-C
• rs369005291
• NM_002785.3:c.914A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002785.3(PSG11):​c.914A>G​(p.Asn305Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PSG11 NM_002785.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32314426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSG11	NM_002785.3	c.914A>G	p.Asn305Ser	missense_variant	Exon 4 of 6	ENST00000320078.12	NP_002776.3
PSG11	NM_001113410.2	c.548A>G	p.Asn183Ser	missense_variant	Exon 3 of 5		NP_001106881.1
PSG11	NM_203287.2	c.548A>G	p.Asn183Ser	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.914A>G	p.Asn305Ser	missense_variant	Exon 4 of 6	2	NM_002785.3	ENSP00000319140.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251078 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135676

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460284 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 726458

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.914A>G (p.N305S) alteration is located in exon 4 (coding exon 4) of the PSG11 gene. This alteration results from a A to G substitution at nucleotide position 914, causing the asparagine (N) at amino acid position 305 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	.;T;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Uncertain	0.90	.;D;D;D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.4	.;M;.;.
PROVEAN	Uncertain	-4.2	D;D;D;.
REVEL	Benign	0.21
Sift	Uncertain	0.020	D;D;D;.
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.96	D;P;D;.
Vest4		0.45
MVP		0.79
ClinPred		0.79	D
GERP RS		0.98
Varity_R		0.17
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs369005291; hg19: chr19-43519318;