Variant 11-101126013-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2

The NM_001271162.2(PGR):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000479 in 1,461,654 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: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PGR
NM_001271162.2 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

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 (HGNC:):

PGR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4 linkuse as main transcript	c.1783A>G	p.Met595Val	missense_variant	2/8	ENST00000325455.10	NP_000917.3	P06401-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10 linkuse as main transcript	c.1783A>G	p.Met595Val	missense_variant	2/8	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461654

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 30, 2021

The c.1783A>G (p.M595V) alteration is located in exon 2 (coding exon 2) of the PGR gene. This alteration results from a A to G substitution at nucleotide position 1783, causing the methionine (M) at amino acid position 595 to be replaced by a valine (V). 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

0.21

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Uncertain

0.57

D;.;.;T;.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.071

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.84

T;D;T;T;D;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.20

T;T;T;T;T;T

MetaSVM

Uncertain

0.13

MutationAssessor

Benign

-1.1

N;.;N;.;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.1

N;N;N;.;.;.

REVEL

Uncertain

0.38

Sift

Benign

0.47

T;T;T;.;.;.

Sift4G

Benign

1.0

T;T;T;T;T;.

Polyphen

0.081

B;.;.;.;.;.

Vest4

0.27

MutPred

0.54

Gain of ubiquitination at K592 (P = 0.187);.;Gain of ubiquitination at K592 (P = 0.187);Gain of ubiquitination at K592 (P = 0.187);Gain of ubiquitination at K592 (P = 0.187);.;

MVP

0.77

ClinPred

0.84

GERP RS

5.4

Varity_R

0.43

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over