chr11-101039138-G-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000926.4(PGR):c.2780C>A(p.Pro927His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,611,292 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
PGR
NM_000926.4 missense
NM_000926.4 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 7.51
Genes affected
PGR (HGNC:8910): (progesterone receptor) This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce several transcript variants, both protein coding and non-protein coding. Two of the isoforms (A and B) are identical except for an additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PGR | NM_000926.4 | c.2780C>A | p.Pro927His | missense_variant | 8/8 | ENST00000325455.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PGR | ENST00000325455.10 | c.2780C>A | p.Pro927His | missense_variant | 8/8 | 1 | NM_000926.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 151682Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000957 AC: 24AN: 250742Hom.: 0 AF XY: 0.0000959 AC XY: 13AN XY: 135544
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GnomAD4 exome AF: 0.000103 AC: 151AN: 1459610Hom.: 0 Cov.: 30 AF XY: 0.000102 AC XY: 74AN XY: 726192
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GnomAD4 genome AF: 0.000132 AC: 20AN: 151682Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4AN XY: 74088
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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 | Sep 26, 2022 | The c.2780C>A (p.P927H) alteration is located in exon 8 (coding exon 8) of the PGR gene. This alteration results from a C to A substitution at nucleotide position 2780, causing the proline (P) at amino acid position 927 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
P;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0517);.;.;
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at