Variant 2-205118988-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001302769.2(PARD3B):c.748G>A(p.Glu250Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,611,798 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

PARD3B
NM_001302769.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.46

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARD3B	NM_001302769.2 linkuse as main transcript	c.748G>A	p.Glu250Lys	missense_variant	7/23	ENST00000406610.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARD3B	ENST00000406610.7 linkuse as main transcript	c.748G>A	p.Glu250Lys	missense_variant	7/23	1	NM_001302769.2	P1	Q8TEW8-1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000687

AC:

AN:

247392

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

134348

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.0000563

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000507

AC:

AN:

1459632

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

726132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000662

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000598

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

Feb 28, 2023

The c.748G>A (p.E250K) alteration is located in exon 7 (coding exon 7) of the PARD3B gene. This alteration results from a G to A substitution at nucleotide position 748, causing the glutamic acid (E) at amino acid position 250 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

0.18

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.35

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.10

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

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.088

MetaRNN

Uncertain

0.46

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

MetaSVM

Uncertain

0.35

MutationAssessor

Uncertain

2.6

M;.;M;M;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.9

D;.;D;D;D;.;.;.

REVEL

Pathogenic

0.72

Sift

Uncertain

0.014

D;.;D;D;D;.;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;.;D;.;.;.

Vest4

0.95

MutPred

0.51

Gain of methylation at E250 (P = 0.0271);Gain of methylation at E250 (P = 0.0271);Gain of methylation at E250 (P = 0.0271);Gain of methylation at E250 (P = 0.0271);Gain of methylation at E250 (P = 0.0271);.;.;.;

MVP

0.94

MPC

0.19

ClinPred

0.80

GERP RS

5.7

Varity_R

0.55

gMVP

0.72

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over