Variant 2-205440432-C-T 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.2804C>T(p.Thr935Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 1,613,938 control chromosomes in the GnomAD database, including 4,312 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.093 ( 886 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3426 hom. )

Consequence

PARD3B
NM_001302769.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.84

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=0.0017732084).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3B	NM_001302769.2 link	c.2804C>T	p.Thr935Ile	missense_variant	20/23	ENST00000406610.7	NP_001289698.1	Q8TEW8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7 link	c.2804C>T	p.Thr935Ile	missense_variant	20/23	1	NM_001302769.2	ENSP00000385848.2		Q8TEW8-1

Frequencies

GnomAD3 genomes

AF:

0.0925

AC:

14067

AN:

152084

Hom.:

883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0755

Gnomad ASJ

AF:

0.0778

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.0462

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0631

Gnomad OTH

AF:

0.0848

GnomAD3 exomes

AF:

0.0569

AC:

14179

AN:

249212

Hom.:

618

AF XY:

0.0541

AC XY:

7319

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.0460

Gnomad ASJ exome

AF:

0.0763

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.0184

Gnomad FIN exome

AF:

0.0436

Gnomad NFE exome

AF:

0.0623

Gnomad OTH exome

AF:

0.0597

GnomAD4 exome

AF:

0.0630

AC:

92157

AN:

1461736

Hom.:

3426

Cov.:

AF XY:

0.0613

AC XY:

44593

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.0496

Gnomad4 ASJ exome

AF:

0.0747

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0188

Gnomad4 FIN exome

AF:

0.0417

Gnomad4 NFE exome

AF:

0.0660

Gnomad4 OTH exome

AF:

0.0668

GnomAD4 genome

AF:

0.0925

AC:

14085

AN:

152202

Hom.:

886

Cov.:

AF XY:

0.0884

AC XY:

6579

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.0754

Gnomad4 ASJ

AF:

0.0778

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0462

Gnomad4 NFE

AF:

0.0631

Gnomad4 OTH

AF:

0.0839

Alfa

AF:

0.0645

Hom.:

896

Bravo

AF:

0.0988

TwinsUK

AF:

0.0655

AC:

243

ALSPAC

AF:

0.0675

AC:

260

ESP6500AA

AF:

0.176

AC:

693

ESP6500EA

AF:

0.0688

AC:

572

ExAC

AF:

0.0582

AC:

7031

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0697

EpiControl

AF:

0.0689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.077

DEOGEN2

Benign

0.00060

T;.;.;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.70

T;T;T;T;T

MetaRNN

Benign

0.0018

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

0.19

N;N;N;.;.

REVEL

Benign

0.089

Sift

Benign

0.43

T;T;T;.;.

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.051

B;B;.;.;.

Vest4

0.056

MPC

0.023

ClinPred

0.0079

GERP RS

4.4

Varity_R

0.045

gMVP

0.15

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