Genetic Variant NM_000926.4:c.1475G>A (chr11-101127596-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000926.4(PGR):c.1475G>A(p.Arg492Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000867 in 1,153,094 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R492L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

PGR
NM_000926.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.24

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.1475G>A	p.Arg492Gln	missense	Exon 1 of 8	NP_000917.3	P06401-1
PGR	NM_001202474.3		c.983G>A	p.Arg328Gln	missense	Exon 1 of 8	NP_001189403.1	P06401-2
PGR	NM_001271161.2		c.983G>A	p.Arg328Gln	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.1475G>A	p.Arg492Gln	missense	Exon 1 of 8	ENSP00000325120.5	P06401-1
PGR	ENST00000263463.9	TSL:1	c.1475G>A	p.Arg492Gln	missense	Exon 1 of 7	ENSP00000263463.5	P06401-5
PGR	ENST00000526300.5	TSL:1	n.1475G>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000436803.1	Q8NG45

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.67e-7

AC:

AN:

1153094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

555736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23258

American (AMR)

AF:

0.00

AC:

AN:

9154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15462

East Asian (EAS)

AF:

0.00

AC:

AN:

26954

South Asian (SAS)

AF:

0.00

AC:

AN:

34578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3744

European-Non Finnish (NFE)

AF:

0.00000103

AC:

AN:

967774

Other (OTH)

AF:

0.00

AC:

AN:

46964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.54

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

2.2

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Uncertain

0.016

Sift4G

Benign

0.62

Polyphen

1.0

Vest4

0.26

MutPred

0.59

Gain of relative solvent accessibility (P = 0.1571)

MVP

0.65

ClinPred

0.89

GERP RS

3.1

Varity_R

0.14

gMVP

0.38

Mutation Taster

=92/8

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