Variant chr1-154959577-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138300.4(PYGO2):c.423G>A(p.Met141Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,456,446 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 6 hom. )

Consequence

PYGO2
NM_138300.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

Variant links:

Genes affected

PYGO2 (HGNC:30257): (pygopus family PHD finger 2) Predicted to enable several functions, including chromatin binding activity; histone acetyltransferase regulator activity; and histone binding activity. Predicted to be involved in kidney development and spermatid nucleus differentiation. Predicted to act upstream of or within several processes, including animal organ development; positive regulation of chromatin binding activity; and regulation of histone H3-K4 methylation. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

PYGO2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007651925).

BS2

High AC in GnomAd4 at 412 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYGO2	NM_138300.4 linkuse as main transcript	c.423G>A	p.Met141Ile	missense_variant	3/3	ENST00000368457.3	NP_612157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGO2	ENST00000368457.3 linkuse as main transcript	c.423G>A	p.Met141Ile	missense_variant	3/3	1	NM_138300.4	ENSP00000357442	P1
PYGO2	ENST00000368456.1 linkuse as main transcript	c.312G>A	p.Met104Ile	missense_variant	3/3	2		ENSP00000357441

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

414

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00640

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00459

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000839

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.00142

AC:

209

AN:

147278

Hom.:

AF XY:

0.00108

AC XY:

AN XY:

79060

show subpopulations

Gnomad AFR exome

AF:

0.00624

Gnomad AMR exome

AF:

0.00311

Gnomad ASJ exome

AF:

0.000775

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000873

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000925

Gnomad OTH exome

AF:

0.00434

GnomAD4 exome

AF:

0.000850

AC:

1109

AN:

1304560

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

515

AN XY:

636288

show subpopulations

Gnomad4 AFR exome

AF:

0.00646

Gnomad4 AMR exome

AF:

0.00393

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000147

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000648

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00271

AC:

412

AN:

151886

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.00635

Gnomad4 AMR

AF:

0.00459

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000839

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00367

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00148

AC:

172

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.070

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0077

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.19

Sift

Uncertain

0.029

D;D

Sift4G

Benign

0.40

T;T

Polyphen

0.0050

B;.

Vest4

0.34

MutPred

0.17

Loss of glycosylation at P140 (P = 0.0873);.;

MVP

0.64

MPC

0.30

ClinPred

0.012

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.30

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over