Variant 19-43024750-A-G details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.272

Variant links:

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 links:

PSG11-AS1 (HGNC:56358): (PSG11, PSG2 and PSG5 antisense RNA 1)

PSG11-AS1 links:

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ACMG classification

Classification made for transcript

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
PSG11	NM_002785.3 linkuse as main transcript	c.371T>C	p.Ile124Thr	missense_variant	2/6	ENST00000320078.12	NP_002776.3
PSG11	NM_001113410.2 linkuse as main transcript	c.64+1559T>C		intron_variant			NP_001106881.1
PSG11	NM_203287.2 linkuse as main transcript	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 linkuse as main transcript	c.371T>C	p.Ile124Thr	missense_variant	2/6	2	NM_002785.3	ENSP00000319140	P2	Q9UQ72-1
PSG11-AS1	ENST00000635495.1 linkuse as main transcript	n.182+47106A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1460490

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726516

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.089

T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0032

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.95

L;.

MutationTaster

Benign

1.0

N;N;N;N

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over