11-101127596-C-T

Variant names:

• chr11-101127596-C-T
• NM_000926.4:c.1475G>A

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1475G>A	p.Arg492Gln	missense_variant	Exon 1 of 8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10	c.1475G>A	p.Arg492Gln	missense_variant	Exon 1 of 8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.67e-7 AC: 1 AN: 1153094 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 555736

Gnomad4 AFR exome AF: 0.00

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: 0.00000103

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Pathogenic	0.54	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.2	N;N;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.016	D;D;.;.
Sift4G	Benign	0.62	T;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.26
MutPred		0.59		Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);
MVP		0.65
ClinPred		0.89	D
GERP RS		3.1
Varity_R		0.14
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-100998327;