Variant 18-80159788-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032510.4(PARD6G):c.1114C>T(p.Pro372Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,288,356 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PARD6G
NM_032510.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20582277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD6G	NM_032510.4 linkuse as main transcript	c.1114C>T	p.Pro372Ser	missense_variant	3/3	ENST00000353265.8	NP_115899.1	Q9BYG4-1
PARD6G-AS1	NR_028339.1 linkuse as main transcript	n.332-2728G>A		intron_variant
PARD6G-AS1	NR_028340.1 linkuse as main transcript	n.331+11534G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD6G	ENST00000353265.8 linkuse as main transcript	c.1114C>T	p.Pro372Ser	missense_variant	3/3	1	NM_032510.4	ENSP00000343144.3		Q9BYG4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1288356

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

630928

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:

0.0000126

Gnomad4 OTH exome

AF:

0.0000378

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Jun 05, 2024

The c.1114C>T (p.P372S) alteration is located in exon 3 (coding exon 3) of the PARD6G gene. This alteration results from a C to T substitution at nucleotide position 1114, causing the proline (P) at amino acid position 372 to be replaced by a serine (S). 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

0.20

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.028

Eigen

Benign

0.038

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.84

M_CAP

Benign

0.0078

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.70

REVEL

Benign

0.095

Sift

Benign

0.22

Sift4G

Benign

0.57

Polyphen

0.48

Vest4

0.17

MutPred

0.29

Gain of phosphorylation at P372 (P = 0.0306);

MVP

0.47

MPC

1.1

ClinPred

0.41

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.083

gMVP

0.21

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