Variant 10-34336232-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001184785.2(PARD3):c.2572A>T(p.Thr858Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0001 in 1,612,222 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

PARD3
NM_001184785.2 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

PARD3 (HGNC:16051): (par-3 family cell polarity regulator) This gene encodes a member of the PARD protein family. PARD family members interact with other PARD family members and other proteins; they affect asymmetrical cell division and direct polarized cell growth. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

PARD3 links:

PARD3 (HGNC:):

PARD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010822564).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3	NM_001184785.2 linkuse as main transcript	c.2572A>T	p.Thr858Ser	missense_variant	18/25	ENST00000374788.8	NP_001171714.1	Q8TEW0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3	ENST00000374788.8 linkuse as main transcript	c.2572A>T	p.Thr858Ser	missense_variant	18/25	1	NM_001184785.2	ENSP00000363920.3		Q8TEW0-2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000255

AC:

AN:

250816

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00337

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000101

AC:

148

AN:

1459992

Hom.:

Cov.:

AF XY:

0.0000936

AC XY:

AN XY:

726362

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00346

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000147

ExAC

AF:

0.000255

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Neural tube defect

Other:1

risk factor, no assertion criteria provided

case-control

Beijing Municipal Key Laboratory, Capital Institute of Pediatrics

May 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.87

DEOGEN2

Benign

0.069

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

Eigen

Benign

-0.087

Eigen_PC

Benign

0.097

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

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

M_CAP

Benign

0.0078

MetaRNN

Benign

0.011

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;.;L;.;L;.;.;.;.;.;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.12

N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.76

P;.;B;B;B;B;B;B;B;B;B

Vest4

0.31

MutPred

0.11

.;.;Loss of phosphorylation at T861 (P = 0.1492);.;Loss of phosphorylation at T861 (P = 0.1492);.;.;.;.;.;.;

MVP

0.70

MPC

0.086

ClinPred

0.10

GERP RS

4.8

Varity_R

0.093

gMVP

0.14

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