Variant 16-29816941-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024516.4(PAGR1):c.416C>G(p.Pro139Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000636 in 1,573,546 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

PAGR1
NM_024516.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

Variant links:

Genes affected

PAGR1 (HGNC:28707): (PAXIP1 associated glutamate rich protein 1) Enables estrogen receptor binding activity. Involved in positive regulation of cell cycle G1/S phase transition; positive regulation of intracellular estrogen receptor signaling pathway; and positive regulation of transcription by RNA polymerase II. Located in nucleus. Part of MLL3/4 complex. [provided by Alliance of Genome Resources, Apr 2022]

PAGR1 links:

ENSG00000280893 (HGNC:):

ENSG00000280893 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
PAGR1	NM_024516.4 linkuse as main transcript	c.416C>G	p.Pro139Arg	missense_variant	1/3	ENST00000320330.8	NP_078792.1	Q9BTK6
MVP-DT	NR_186424.1 linkuse as main transcript	n.246+2599G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PAGR1	ENST00000320330.8 linkuse as main transcript	c.416C>G	p.Pro139Arg	missense_variant	1/3	1	NM_024516.4	ENSP00000326519.6	Q9BTK6
ENSG00000280893	ENST00000609618.2 linkuse as main transcript	n.*357C>G		non_coding_transcript_exon_variant	4/6	5		ENSP00000476774.2	A0A0G2JLL6
ENSG00000280893	ENST00000609618.2 linkuse as main transcript	n.*357C>G		3_prime_UTR_variant	4/6	5		ENSP00000476774.2	A0A0G2JLL6
MVP-DT	ENST00000569039.5 linkuse as main transcript	n.245+2599G>C		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

185112

Hom.:

AF XY:

0.0000200

AC XY:

AN XY:

100214

show subpopulations

Gnomad AFR exome

AF:

0.000272

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000563

AC:

AN:

1421426

Hom.:

Cov.:

AF XY:

0.00000710

AC XY:

AN XY:

703992

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

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:

0.00000640

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000230

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000250

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.416C>G (p.P139R) alteration is located in exon 1 (coding exon 1) of the PAGR1 gene. This alteration results from a C to G substitution at nucleotide position 416, causing the proline (P) at amino acid position 139 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0088

MetaRNN

Uncertain

0.61

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.8

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.17

Sift

Benign

0.089

Sift4G

Benign

0.071

Polyphen

1.0

Vest4

0.69

MVP

0.50

ClinPred

0.95

GERP RS

5.2

Varity_R

0.41

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over