11-101062681-C-T

Variant names:

• chr11-101062681-C-T
• rs1042838
• NM_000926.4:c.1978G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000926.4(PGR):​c.1978G>A​(p.Val660Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGR NM_000926.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15912196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	NM_000926.4	MANE Select	c.1978G>A	p.Val660Met	missense	Exon 4 of 8	NP_000917.3	P06401-1
	PGR	NM_001202474.3		c.1486G>A	p.Val496Met	missense	Exon 4 of 8	NP_001189403.1	P06401-2
	PGR	NM_001271162.2		c.196G>A	p.Val66Met	missense	Exon 4 of 8	NP_001258091.1	P06401-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGR	ENST00000325455.10	TSL:1 MANE Select	c.1978G>A	p.Val660Met	missense	Exon 4 of 8	ENSP00000325120.5	P06401-1
	PGR	ENST00000263463.9	TSL:1	c.1907-11113G>A		intron	N/A	ENSP00000263463.5	P06401-5
	PGR	ENST00000528960.5	TSL:1	n.1861G>A		non_coding_transcript_exon	Exon 3 of 7	ENSP00000432914.1	Q8NG44

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.71
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.19
Sift	Benign	0.081	T
Sift4G	Benign	0.16	T
Polyphen		0.015	B
Vest4		0.20
MutPred		0.23		Gain of disorder (P = 0.0658)
MVP		0.80
ClinPred		0.22	T
GERP RS		4.5
Varity_R		0.051
gMVP		0.16
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: rs1042838; hg19: chr11-100933412;