Variant 18-80160089-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032510.4(PARD6G):c.813C>G(p.Asp271Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,598,110 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

PARD6G
NM_032510.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

PARD6G (HGNC:16076): (par-6 family cell polarity regulator gamma) Predicted to enable protein kinase C binding activity. Predicted to be involved in centrosome cycle; establishment or maintenance of cell polarity; and regulation of cellular localization. Predicted to be located in cytosol and plasma membrane. Predicted to be part of protein-containing complex. Predicted to be active in apical plasma membrane; cell cortex; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PARD6G links:

PARD6G-AS1 (HGNC:):

PARD6G-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02460283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD6G	NM_032510.4 linkuse as main transcript	c.813C>G	p.Asp271Glu	missense_variant	3/3	ENST00000353265.8	NP_115899.1	Q9BYG4-1
PARD6G-AS1	NR_028339.1 linkuse as main transcript	n.332-2427G>C		intron_variant
PARD6G-AS1	NR_028340.1 linkuse as main transcript	n.331+11835G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD6G	ENST00000353265.8 linkuse as main transcript	c.813C>G	p.Asp271Glu	missense_variant	3/3	1	NM_032510.4	ENSP00000343144.3		Q9BYG4-1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000325

AC:

AN:

227700

Hom.:

AF XY:

0.000387

AC XY:

AN XY:

124064

show subpopulations

Gnomad AFR exome

AF:

0.0000685

Gnomad AMR exome

AF:

0.0000600

Gnomad ASJ exome

AF:

0.00227

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000164

Gnomad NFE exome

AF:

0.000445

Gnomad OTH exome

AF:

0.000532

GnomAD4 exome

AF:

0.000219

AC:

316

AN:

1445816

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

173

AN XY:

718048

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00275

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000182

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.000284

GnomAD4 genome

AF:

0.000355

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000440

Hom.:

Bravo

AF:

0.000332

ExAC

AF:

0.000333

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

Apr 08, 2022

The c.813C>G (p.D271E) alteration is located in exon 3 (coding exon 3) of the PARD6G gene. This alteration results from a C to G substitution at nucleotide position 813, causing the aspartic acid (D) at amino acid position 271 to be replaced by a glutamic acid (E). 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

0.099

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.027

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.30

M_CAP

Benign

0.021

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.85

REVEL

Benign

0.097

Sift

Benign

0.16

Sift4G

Benign

0.43

Polyphen

0.37

Vest4

0.31

MutPred

0.23

Gain of glycosylation at P269 (P = 0.095);

MVP

0.44

MPC

1.1

ClinPred

0.031

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.10

gMVP

0.38

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