NM_001098201.3:c.107C>T

Variant names:

• chr7-1091835-C-T
• rs767361838
• NM_001098201.3:c.107C>T

Variant summary

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

The NM_001098201.3(GPER1):​c.107C>T​(p.Pro36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,455,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P36R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: GPER1 NM_001098201.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.415
• Publications: 0 publications found

Genes affected

GPER1 (HGNC:4485): (G protein-coupled estrogen receptor 1) This gene encodes a multi-pass membrane protein that localizes to the endoplasmic reticulum and a member of the G-protein coupled receptor 1 family. This receptor binds estrogen and activates multiple downstream signaling pathways, leading to stimulation of adenylate cyclase and an increase in cyclic AMP levels, while also promoting intracellular calcium mobilization and synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus. This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen. This receptor has been shown to play a role in diverse biological processes, including bone and nervous system development, metabolism, cognition, male fertility and uterine function. [provided by RefSeq, Aug 2017]

CHLSN (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098201.3. 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
	GPER1	NM_001098201.3	MANE Select	c.107C>T	p.Pro36Leu	missense	Exon 2 of 2	NP_001091671.1	Q99527
	CHLSN	NM_001318252.2	MANE Select	c.129+35422G>A		intron	N/A	NP_001305181.1	Q9BRJ6
	GPER1	NM_001039966.2		c.107C>T	p.Pro36Leu	missense	Exon 3 of 3	NP_001035055.1	Q99527

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPER1	ENST00000397088.4	TSL:1 MANE Select	c.107C>T	p.Pro36Leu	missense	Exon 2 of 2	ENSP00000380277.3	Q99527
	GPER1	ENST00000297469.3	TSL:1	c.107C>T	p.Pro36Leu	missense	Exon 2 of 2	ENSP00000297469.3	Q99527
	CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.129+35422G>A		intron	N/A	ENSP00000380286.3	Q9BRJ6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 249032 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000220 AC: 32 AN: 1455488 Hom.: 0 Cov.: 35 AF XY: 0.0000277 AC XY: 20 AN XY: 722746

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.0000897 AC: 4 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.0000466 AC: 4 AN: 85926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000190 AC: 21 AN: 1107288

Other (OTH) AF: 0.0000499 AC: 3 AN: 60118

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.11
DANN	Benign	0.62
DEOGEN2	Benign	0.049	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.40	N
PhyloP100		-0.41
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.13
Sift	Benign	0.35	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.093
MutPred		0.43		Loss of disorder (P = 0.0346)
MVP		0.24
MPC		0.42
ClinPred		0.020	T
GERP RS		-2.3
Varity_R		0.022
gMVP		0.34
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.30		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs767361838; hg19: chr7-1131471;