Variant 20-50731812-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032521.3(PARD6B):c.26C>T(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000813 in 1,462,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

PARD6B
NM_032521.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07568815).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD6B	NM_032521.3 linkuse as main transcript	c.26C>T	p.Ala9Val	missense_variant	1/3	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.26C>T	p.Ala9Val	missense_variant	1/3	1	NM_032521.3	ENSP00000360672.2		Q9BYG5-1
PARD6B	ENST00000396039.1 linkuse as main transcript	c.26C>T	p.Ala9Val	missense_variant	1/3	1		ENSP00000379354.1		Q9BYG5-2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000800

AC:

AN:

75026

Hom.:

AF XY:

0.0000692

AC XY:

AN XY:

43332

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000219

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000839

AC:

110

AN:

1310684

Hom.:

Cov.:

AF XY:

0.0000882

AC XY:

AN XY:

646006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000100

Gnomad4 OTH exome

AF:

0.0000920

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000389

AC:

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

Nov 25, 2024

The c.26C>T (p.A9V) alteration is located in exon 1 (coding exon 1) of the PARD6B gene. This alteration results from a C to T substitution at nucleotide position 26, causing the alanine (A) at amino acid position 9 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0086

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.63

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.83

L;L

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.84

N;N

REVEL

Benign

0.026

Sift

Benign

0.20

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0020

B;.

Vest4

0.14

MutPred

0.17

Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);

MVP

0.16

MPC

0.32

ClinPred

0.063

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.088

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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