Variant chr16-29816913-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024516.4(PAGR1):c.388G>A(p.Glu130Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PAGR1
NM_024516.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.06

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18951094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAGR1	NM_024516.4 linkuse as main transcript	c.388G>A	p.Glu130Lys	missense_variant	1/3	ENST00000320330.8	NP_078792.1	Q9BTK6
MVP-DT	NR_186424.1 linkuse as main transcript	n.246+2627C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PAGR1	ENST00000320330.8 linkuse as main transcript	c.388G>A	p.Glu130Lys	missense_variant	1/3	1	NM_024516.4	ENSP00000326519.6	Q9BTK6
ENSG00000280893	ENST00000609618.2 linkuse as main transcript	n.*329G>A		non_coding_transcript_exon_variant	4/6	5		ENSP00000476774.2	A0A0G2JLL6
ENSG00000280893	ENST00000609618.2 linkuse as main transcript	n.*329G>A		3_prime_UTR_variant	4/6	5		ENSP00000476774.2	A0A0G2JLL6
MVP-DT	ENST00000569039.5 linkuse as main transcript	n.245+2627C>T		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1412400

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699042

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 15, 2023

The c.388G>A (p.E130K) 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 388, causing the glutamic acid (E) at amino acid position 130 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

0.11

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.013

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0052

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.0

REVEL

Benign

0.053

Sift

Benign

0.57

Sift4G

Benign

0.17

Polyphen

0.78

Vest4

0.29

MutPred

0.24

Gain of methylation at E130 (P = 0.0017);

MVP

0.043

ClinPred

0.94

GERP RS

4.2

Varity_R

0.21

gMVP

0.29

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over