Variant 11-101127633-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000926.4(PGR):c.1438T>G(p.Cys480Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,366,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

PGR
NM_000926.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.432

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2209768).

BS2

High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4 linkuse as main transcript	c.1438T>G	p.Cys480Gly	missense_variant	1/8	ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10 linkuse as main transcript	c.1438T>G	p.Cys480Gly	missense_variant	1/8	1	NM_000926.4	P1	P06401-1

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000412

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000481

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1214762

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

590856

show subpopulations

Gnomad4 AFR exome

AF:

0.000490

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000204

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000130

Gnomad4 OTH exome

AF:

0.0000201

GnomAD4 genome

AF:

0.000119

AC:

AN:

151246

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

73862

show subpopulations

Gnomad4 AFR

AF:

0.000412

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.0000113

AC:

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

Aug 12, 2021

The c.1438T>G (p.C480G) alteration is located in exon 1 (coding exon 1) of the PGR gene. This alteration results from a T to G substitution at nucleotide position 1438, causing the cysteine (C) at amino acid position 480 to be replaced by a glycine (G). 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

Benign

0.12

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.22

T;.;T;.

Eigen

Benign

-0.013

Eigen_PC

Benign

0.030

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.63

T;T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;.;.

MutationTaster

Benign

0.96

D;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.1

D;D;.;.

REVEL

Benign

0.15

Sift

Benign

0.12

T;D;.;.

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.95

P;.;.;.

Vest4

0.22

MutPred

0.69

Loss of catalytic residue at P479 (P = 0.0244);Loss of catalytic residue at P479 (P = 0.0244);Loss of catalytic residue at P479 (P = 0.0244);Loss of catalytic residue at P479 (P = 0.0244);

MVP

0.61

ClinPred

0.69

GERP RS

2.9

Varity_R

0.16

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over