Genetic Variant PGR:p.Glu395Ala (chr11-101127887-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000926.4(PGR):c.1184A>C(p.Glu395Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E395G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PGR
NM_000926.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Publications

0 publications found

Variant links:

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]

PGR links:

PGR-AS1 (HGNC:52650): (PGR antisense RNA 1)

PGR-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23462671).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGR	NM_000926.4	MANE Select	c.1184A>C	p.Glu395Ala	missense	Exon 1 of 8	NP_000917.3	P06401-1
PGR	NM_001202474.3		c.692A>C	p.Glu231Ala	missense	Exon 1 of 8	NP_001189403.1	P06401-2
PGR	NM_001271161.2		c.692A>C	p.Glu231Ala	missense	Exon 1 of 7	NP_001258090.1	P06401

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGR	ENST00000325455.10	TSL:1 MANE Select	c.1184A>C	p.Glu395Ala	missense	Exon 1 of 8	ENSP00000325120.5	P06401-1
PGR	ENST00000263463.9	TSL:1	c.1184A>C	p.Glu395Ala	missense	Exon 1 of 7	ENSP00000263463.5	P06401-5
PGR	ENST00000526300.5	TSL:1	n.1184A>C		non_coding_transcript_exon	Exon 1 of 6	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1439382

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716952

African (AFR)

AF:

0.00

AC:

AN:

32376

American (AMR)

AF:

0.00

AC:

AN:

43854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25130

East Asian (EAS)

AF:

0.00

AC:

AN:

37194

South Asian (SAS)

AF:

0.00

AC:

AN:

85984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103178

Other (OTH)

AF:

0.00

AC:

AN:

58834

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.20

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

2.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.2

REVEL

Benign

0.054

Sift

Benign

0.10

Sift4G

Benign

0.25

Polyphen

0.64

Vest4

0.22

MutPred

0.44

Gain of helix (P = 0.062)

MVP

0.34

ClinPred

0.49

GERP RS

2.8

Varity_R

0.063

gMVP

0.25

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over