Variant rs2289025 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001302769.2(PARD3B):c.575G>A(p.Arg192Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 1,565,804 control chromosomes in the GnomAD database, including 311,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.61 ( 28369 hom., cov: 32)

Exomes 𝑓: 0.63 ( 282777 hom. )

Consequence

PARD3B
NM_001302769.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

Variant links:

Genes affected

PARD3B (HGNC:14446): (par-3 family cell polarity regulator beta) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in several processes, including establishment of cell polarity; establishment of centrosome localization; and establishment or maintenance of epithelial cell apical/basal polarity. Located in cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

PARD3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5535625E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3B	NM_001302769.2 linkuse as main transcript	c.575G>A	p.Arg192Lys	missense_variant	5/23	ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7 linkuse as main transcript	c.575G>A	p.Arg192Lys	missense_variant	5/23	1	NM_001302769.2	ENSP00000385848	P1	Q8TEW8-1

Frequencies

GnomAD3 genomes

AF:

0.605

AC:

91963

AN:

151894

Hom.:

28342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.698

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.798

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.611

GnomAD3 exomes

AF:

0.650

AC:

161777

AN:

248738

Hom.:

53478

AF XY:

0.650

AC XY:

87768

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.527

Gnomad AMR exome

AF:

0.768

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.791

Gnomad SAS exome

AF:

0.716

Gnomad FIN exome

AF:

0.556

Gnomad NFE exome

AF:

0.620

Gnomad OTH exome

AF:

0.622

GnomAD4 exome

AF:

0.629

AC:

889855

AN:

1413792

Hom.:

282777

Cov.:

AF XY:

0.631

AC XY:

445481

AN XY:

705864

show subpopulations

Gnomad4 AFR exome

AF:

0.520

Gnomad4 AMR exome

AF:

0.756

Gnomad4 ASJ exome

AF:

0.551

Gnomad4 EAS exome

AF:

0.804

Gnomad4 SAS exome

AF:

0.714

Gnomad4 FIN exome

AF:

0.554

Gnomad4 NFE exome

AF:

0.620

Gnomad4 OTH exome

AF:

0.625

GnomAD4 genome

AF:

0.605

AC:

92039

AN:

152012

Hom.:

28369

Cov.:

AF XY:

0.611

AC XY:

45407

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.699

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.797

Gnomad4 SAS

AF:

0.721

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.620

Gnomad4 OTH

AF:

0.614

Alfa

AF:

0.624

Hom.:

71637

Bravo

AF:

0.613

TwinsUK

AF:

0.632

AC:

2344

ALSPAC

AF:

0.624

AC:

2403

ESP6500AA

AF:

0.543

AC:

1988

ESP6500EA

AF:

0.624

AC:

5112

ExAC

AF:

0.644

AC:

77746

Asia WGS

AF:

0.753

AC:

2621

AN:

3478

EpiCase

AF:

0.624

EpiControl

AF:

0.623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.66

DANN

Benign

0.48

DEOGEN2

Benign

0.00057

T;T;.;.;.;.;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00045

LIST_S2

Benign

0.039

T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0000016

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.85

N;.;N;N;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

0.020

N;.;N;N;N;.;.;.

REVEL

Benign

0.013

Sift

Benign

1.0

T;.;T;T;T;.;.;.

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T

Polyphen

0.0

B;.;B;.;B;.;.;.

Vest4

0.045

MPC

0.022

ClinPred

0.0014

GERP RS

0.10

Varity_R

0.042

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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