Variant chr16-29816742-A-C 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.217A>C(p.Ser73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000967 in 1,447,510 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: not found (cov: 32)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

PAGR1
NM_024516.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.467

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=0.051846325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAGR1	NM_024516.4 linkuse as main transcript	c.217A>C	p.Ser73Arg	missense_variant	1/3	ENST00000320330.8	NP_078792.1	Q9BTK6
MVP-DT	NR_186424.1 linkuse as main transcript	n.246+2798T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PAGR1	ENST00000320330.8 linkuse as main transcript	c.217A>C	p.Ser73Arg	missense_variant	1/3	1	NM_024516.4	ENSP00000326519.6	Q9BTK6
ENSG00000280893	ENST00000609618.2 linkuse as main transcript	n.*158A>C		non_coding_transcript_exon_variant	4/6	5		ENSP00000476774.2	A0A0G2JLL6
ENSG00000280893	ENST00000609618.2 linkuse as main transcript	n.*158A>C		3_prime_UTR_variant	4/6	5		ENSP00000476774.2	A0A0G2JLL6
MVP-DT	ENST00000569039.5 linkuse as main transcript	n.245+2798T>G		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000188

AC:

AN:

213268

Hom.:

AF XY:

0.0000171

AC XY:

AN XY:

117216

show subpopulations

Gnomad AFR exome

AF:

0.0000824

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:

0.0000543

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

AF:

0.00000967

AC:

AN:

1447510

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

719020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.000177

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000640

Hom.:

ExAC

AF:

0.0000417

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

Mar 21, 2023

The c.217A>C (p.S73R) alteration is located in exon 1 (coding exon 1) of the PAGR1 gene. This alteration results from a A to C substitution at nucleotide position 217, causing the serine (S) at amino acid position 73 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

Benign

0.099

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.2

DANN

Uncertain

0.97

DEOGEN2

Benign

0.16

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.50

M_CAP

Benign

0.0033

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.32

REVEL

Benign

0.029

Sift

Benign

0.14

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.091

MutPred

0.10

Loss of phosphorylation at S73 (P = 0.0047);

MVP

0.082

ClinPred

0.044

GERP RS

-5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.16

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

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