dbSNP rs750168894: PGR:p.Asn643Tyr (chr11-101062732-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000926.4(PGR):c.1927A>T(p.Asn643Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. N643D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PGR
NM_000926.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.45

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39798236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.1927A>T	p.Asn643Tyr	missense_variant	Exon 4 of 8	ENST00000325455.10	NP_000917.3	P06401-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10 link	c.1927A>T	p.Asn643Tyr	missense_variant	Exon 4 of 8	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459824

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33312

American (AMR)

AF:

0.00

AC:

AN:

44378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

85858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111510

Other (OTH)

AF:

0.00

AC:

AN:

60304

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

D;.;.;T

Eigen

Benign

0.068

Eigen_PC

Benign

0.028

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;T;D;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.40

T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.9

M;.;.;.

PhyloP100

3.5

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.9

D;D;.;.

REVEL

Benign

0.17

Sift

Uncertain

0.010

D;D;.;.

Sift4G

Uncertain

0.0080

D;D;D;.

Polyphen

0.99

D;.;.;.

Vest4

0.40

MutPred

0.42

Loss of disorder (P = 0.027);.;.;.;

MVP

0.74

ClinPred

0.99

GERP RS

4.1

Varity_R

0.28

gMVP

0.39

Mutation Taster

=74/26

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over