19-43024750-A-G

Variant summary

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

The NM_002785.3(PSG11):ā€‹c.371T>Cā€‹(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 (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.000023 ( 1 hom. )

Consequence

PSG11
NM_002785.3 missense

Scores

5
13

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

Genome browser will be placed here

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 UniProt
PSG11NM_002785.3 linkuse as main transcriptc.371T>C p.Ile124Thr missense_variant 2/6 ENST00000320078.12 NP_002776.3
PSG11NM_001113410.2 linkuse as main transcriptc.64+1559T>C intron_variant NP_001106881.1
PSG11NM_203287.2 linkuse as main transcriptc.64+1559T>C intron_variant NP_976032.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSG11ENST00000320078.12 linkuse as main transcriptc.371T>C p.Ile124Thr missense_variant 2/62 NM_002785.3 ENSP00000319140 P2Q9UQ72-1
PSG11-AS1ENST00000635495.1 linkuse as main transcriptn.182+47106A>G intron_variant, non_coding_transcript_variant 5

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
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.:
31

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 submitterclinical testingAmbry GeneticsNov 29, 2023The 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;.
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
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; API