Variant 16-67662462-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001037281.2(PARD6A):c.853G>A(p.Val285Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,613,598 control chromosomes in the GnomAD database, including 1,337 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 95 hom., cov: 33)

Exomes 𝑓: 0.038 ( 1242 hom. )

Consequence

PARD6A
NM_001037281.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

PARD6A (HGNC:15943): (par-6 family cell polarity regulator alpha) This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cell membrane protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. The protein also has a role in the epithelial-to-mesenchymal transition (EMT) that characterizes the invasive phenotype associated with metastatic carcinomas. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

PARD6A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020911098).

BP6

Variant 16-67662462-G-A is Benign according to our data. Variant chr16-67662462-G-A is described in ClinVar as [Benign]. Clinvar id is 3056133.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARD6A	NM_001037281.2 linkuse as main transcript	c.853G>A	p.Val285Ile	missense_variant	3/3	ENST00000458121.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARD6A	ENST00000458121.7 linkuse as main transcript	c.853G>A	p.Val285Ile	missense_variant	3/3	1	NM_001037281.2	A1	Q9NPB6-2
PARD6A	ENST00000219255.3 linkuse as main transcript	c.856G>A	p.Val286Ile	missense_variant	3/3	1		P4	Q9NPB6-1
PARD6A	ENST00000602551.5 linkuse as main transcript	c.766G>A	p.Val256Ile	missense_variant	3/3	5
PARD6A	ENST00000602727.1 linkuse as main transcript	n.1013G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0297

AC:

4517

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00910

Gnomad FIN

AF:

0.0252

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0415

Gnomad OTH

AF:

0.0463

GnomAD3 exomes

AF:

0.0313

AC:

7832

AN:

250442

Hom.:

178

AF XY:

0.0319

AC XY:

4320

AN XY:

135578

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.0236

Gnomad ASJ exome

AF:

0.0607

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0118

Gnomad FIN exome

AF:

0.0259

Gnomad NFE exome

AF:

0.0448

Gnomad OTH exome

AF:

0.0426

GnomAD4 exome

AF:

0.0381

AC:

55710

AN:

1461254

Hom.:

1242

Cov.:

AF XY:

0.0376

AC XY:

27308

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.0118

Gnomad4 AMR exome

AF:

0.0245

Gnomad4 ASJ exome

AF:

0.0618

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.0276

Gnomad4 NFE exome

AF:

0.0423

Gnomad4 OTH exome

AF:

0.0410

GnomAD4 genome

AF:

0.0297

AC:

4522

AN:

152344

Hom.:

Cov.:

AF XY:

0.0282

AC XY:

2098

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.0351

Gnomad4 ASJ

AF:

0.0576

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00911

Gnomad4 FIN

AF:

0.0252

Gnomad4 NFE

AF:

0.0415

Gnomad4 OTH

AF:

0.0458

Alfa

AF:

0.0417

Hom.:

268

Bravo

AF:

0.0289

TwinsUK

AF:

0.0464

AC:

172

ALSPAC

AF:

0.0428

AC:

165

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.0415

AC:

357

ExAC

AF:

0.0316

AC:

3839

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0438

EpiControl

AF:

0.0499

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PARD6A-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.92

D;D

PrimateAI

Benign

0.36

Sift4G

Benign

0.53

T;T;T

Polyphen

0.0020, 0.0010

.;B;B

Vest4

0.059

MPC

0.33

ClinPred

0.013

GERP RS

4.3

Varity_R

0.060

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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