rs778346200

Variant names:

• chr11-101127612-C-A
• rs778346200
• NM_000926.4:c.1459G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-101127612-C-A
• chr11-101127612-C-G
• chr11-101127612-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000926.4(PGR):​c.1459G>T​(p.Gly487Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000954 in 1,152,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. G487S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000095 (0 hom.)
• Consequence: PGR NM_000926.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 2 publications found

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-AS1 (HGNC:52650): (PGR antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25759375).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4	c.1459G>T	p.Gly487Cys	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.1459G>T	p.Gly487Cys	missense_variant	Exon 1 of 8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000954 AC: 11 AN: 1152890 Hom.: 0 Cov.: 31 AF XY: 0.0000108 AC XY: 6 AN XY: 555348

African (AFR) AF: 0.00 AC: 0 AN: 23220

American (AMR) AF: 0.00 AC: 0 AN: 9042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15450

East Asian (EAS) AF: 0.00 AC: 0 AN: 27022

South Asian (SAS) AF: 0.00 AC: 0 AN: 34312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3886

European-Non Finnish (NFE) AF: 0.0000114 AC: 11 AN: 968016

Other (OTH) AF: 0.00 AC: 0 AN: 46966

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;.;T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N;.;.
PhyloP100		-0.12
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.3	N;N;.;.
REVEL	Benign	0.086
Sift	Uncertain	0.0030	D;D;.;.
Sift4G	Uncertain	0.021	D;D;T;T
Polyphen		0.90	P;.;.;.
Vest4		0.16
MutPred		0.60		Loss of glycosylation at S486 (P = 0.0523);Loss of glycosylation at S486 (P = 0.0523);Loss of glycosylation at S486 (P = 0.0523);Loss of glycosylation at S486 (P = 0.0523);
MVP		0.28
ClinPred		0.51	D
GERP RS		1.8
Varity_R		0.23
gMVP		0.31
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs778346200; hg19: chr11-100998343;