Variant chr20-50749692-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032521.3(PARD6B):c.323C>T(p.Thr108Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,609,946 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 100 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 81 hom. )

Consequence

PARD6B
NM_032521.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.47

Variant links:

Genes affected

PARD6B (HGNC:16245): (par-6 family cell polarity regulator beta) This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain, an OPR domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cytoplasmic protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. [provided by RefSeq, Jul 2008]

PARD6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003006637).

BP6

Variant 20-50749692-C-T is Benign according to our data. Variant chr20-50749692-C-T is described in ClinVar as [Benign]. Clinvar id is 770002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD6B	NM_032521.3 linkuse as main transcript	c.323C>T	p.Thr108Met	missense_variant	3/3	ENST00000371610.7	NP_115910.1	Q9BYG5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD6B	ENST00000371610.7 linkuse as main transcript	c.323C>T	p.Thr108Met	missense_variant	3/3	1	NM_032521.3	ENSP00000360672.2		Q9BYG5-1
PARD6B	ENST00000396039.1 linkuse as main transcript	c.290-6993C>T		intron_variant		1		ENSP00000379354.1		Q9BYG5-2

Frequencies

GnomAD3 genomes

AF:

0.0198

AC:

3016

AN:

152084

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0689

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.00546

AC:

1350

AN:

247356

Hom.:

AF XY:

0.00416

AC XY:

556

AN XY:

133752

show subpopulations

Gnomad AFR exome

AF:

0.0722

Gnomad AMR exome

AF:

0.00435

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00198

AC:

2891

AN:

1457744

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1218

AN XY:

725126

show subpopulations

Gnomad4 AFR exome

AF:

0.0673

Gnomad4 AMR exome

AF:

0.00505

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.00439

GnomAD4 genome

AF:

0.0198

AC:

3021

AN:

152202

Hom.:

100

Cov.:

AF XY:

0.0192

AC XY:

1431

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0689

Gnomad4 AMR

AF:

0.00758

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00281

Hom.:

Bravo

AF:

0.0224

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0715

AC:

315

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00654

AC:

794

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.1

REVEL

Benign

0.18

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.38

MVP

0.55

MPC

0.95

ClinPred

0.031

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.071

gMVP

0.61

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