Variant 16-29816697-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024516.4(PAGR1):c.172G>A(p.Glu58Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000841 in 1,605,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

PAGR1
NM_024516.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03489521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAGR1	NM_024516.4 linkuse as main transcript	c.172G>A	p.Glu58Lys	missense_variant	1/3	ENST00000320330.8	NP_078792.1	Q9BTK6
MVP-DT	NR_186424.1 linkuse as main transcript	n.246+2843C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PAGR1	ENST00000320330.8 linkuse as main transcript	c.172G>A	p.Glu58Lys	missense_variant	1/3	1	NM_024516.4	ENSP00000326519.6	Q9BTK6
ENSG00000280893	ENST00000609618.2 linkuse as main transcript	n.*113G>A		non_coding_transcript_exon_variant	4/6	5		ENSP00000476774.2	A0A0G2JLL6
ENSG00000280893	ENST00000609618.2 linkuse as main transcript	n.*113G>A		3_prime_UTR_variant	4/6	5		ENSP00000476774.2	A0A0G2JLL6
MVP-DT	ENST00000569039.5 linkuse as main transcript	n.245+2843C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000883

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000759

AC:

AN:

237022

Hom.:

AF XY:

0.0000844

AC XY:

AN XY:

130382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000118

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:

0.000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000867

AC:

126

AN:

1453088

Hom.:

Cov.:

AF XY:

0.0000679

AC XY:

AN XY:

721550

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000902

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:

0.000107

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000240

AC:

ExAC

AF:

0.0000995

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

Sep 25, 2023

The c.172G>A (p.E58K) alteration is located in exon 1 (coding exon 1) of the PAGR1 gene. This alteration results from a G to A substitution at nucleotide position 172, causing the glutamic acid (E) at amino acid position 58 to be replaced by a lysine (K). 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

Benign

0.072

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.75

M_CAP

Benign

0.0028

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.49

REVEL

Benign

0.070

Sift

Benign

0.85

Sift4G

Benign

0.22

Polyphen

0.034

Vest4

0.12

MVP

0.082

ClinPred

0.062

GERP RS

4.7

Varity_R

0.19

gMVP

0.18

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