Genetic Variant PAGR1:p.Ala11Glu (chr16-29816557-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024516.4(PAGR1):c.32C>A(p.Ala11Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PAGR1
NM_024516.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.264

Publications

0 publications found

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:

MVP-DT (HGNC:56029): (MVP divergent transcript)

MVP-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.12937438).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024516.4. 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
	PAGR1	NM_024516.4	MANE Select	c.32C>A	p.Ala11Glu	missense	Exon 1 of 3	NP_078792.1	Q9BTK6
	MVP-DT	NR_186424.1		n.246+2983G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAGR1	ENST00000320330.8	TSL:1 MANE Select	c.32C>A	p.Ala11Glu	missense	Exon 1 of 3	ENSP00000326519.6	Q9BTK6
ENSG00000280893	ENST00000609618.2	TSL:5	n.1053C>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000476774.2	A0A0G2JLL6
MVP-DT	ENST00000569039.5	TSL:2	n.245+2983G>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1358704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

664684

African (AFR)

AF:

0.00

AC:

AN:

30068

American (AMR)

AF:

0.00

AC:

AN:

28370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19742

East Asian (EAS)

AF:

0.00

AC:

AN:

38656

South Asian (SAS)

AF:

0.00

AC:

AN:

69350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4244

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1064016

Other (OTH)

AF:

0.00

AC:

AN:

55774

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.21

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.65

M_CAP

Benign

0.0039

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

PhyloP100

0.26

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.58

REVEL

Benign

0.049

Sift

Uncertain

0.0070

Sift4G

Benign

1.0

Polyphen

0.16

Vest4

0.28

MutPred

0.17

Gain of solvent accessibility (P = 0.0145)

MVP

0.068

ClinPred

0.21

GERP RS

2.4

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.21

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over