19-43024750-A-G

Position:

• chr19-43024750-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002785.3(PSG11):​c.371T>C​(p.Ile124Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,460,490 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000023 (1 hom.)
• Consequence: PSG11 NM_002785.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.272

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSG11	NM_002785.3	c.371T>C	p.Ile124Thr	missense_variant	2/6	ENST00000320078.12	NP_002776.3
PSG11	NM_001113410.2	c.64+1559T>C		intron_variant			NP_001106881.1
PSG11	NM_203287.2	c.64+1559T>C		intron_variant			NP_976032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSG11	ENST00000320078.12	c.371T>C	p.Ile124Thr	missense_variant	2/6	2	NM_002785.3	ENSP00000319140.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1460490 Hom.: 1 Cov.: 45 AF XY: 0.0000220 AC XY: 16 AN XY: 726516

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: 0.0000297

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2023

The c.371T>C (p.I124T) alteration is located in exon 2 (coding exon 2) of the PSG11 gene. This alteration results from a T to C substitution at nucleotide position 371, causing the isoleucine (I) at amino acid position 124 to be replaced by a threonine (T). 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	0.37
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.089	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.95	L;.
PROVEAN	Uncertain	-3.7	D;.
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D;.
Sift4G	Benign	0.40	T;T
Polyphen		0.75	P;.
Vest4		0.30
MutPred		0.75		Gain of disorder (P = 0.036);Gain of disorder (P = 0.036);
MVP		0.67
ClinPred		0.38	T
GERP RS		0.93
Varity_R		0.29
gMVP		0.097

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-43528902;