chr18-80159937-C-T

Variant summary

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

The NM_032510.4(PARD6G):​c.965G>A​(p.Ser322Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,353,034 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: not found (cov: 33)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

PARD6G
NM_032510.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.714
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]

Genome browser will be placed here

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=0.12251449).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PARD6GNM_032510.4 linkuse as main transcriptc.965G>A p.Ser322Asn missense_variant 3/3 ENST00000353265.8 NP_115899.1 Q9BYG4-1
PARD6G-AS1NR_028339.1 linkuse as main transcriptn.332-2579C>T intron_variant
PARD6G-AS1NR_028340.1 linkuse as main transcriptn.331+11683C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PARD6GENST00000353265.8 linkuse as main transcriptc.965G>A p.Ser322Asn missense_variant 3/31 NM_032510.4 ENSP00000343144.3 Q9BYG4-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000960
AC:
1
AN:
104214
Hom.:
0
AF XY:
0.0000173
AC XY:
1
AN XY:
57956
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:
0.0000228
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000318
AC:
43
AN:
1353034
Hom.:
0
Cov.:
31
AF XY:
0.0000180
AC XY:
12
AN XY:
667140
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:
0.0000393
Gnomad4 OTH exome
AF:
0.0000178
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsSep 02, 2024The c.965G>A (p.S322N) alteration is located in exon 3 (coding exon 3) of the PARD6G gene. This alteration results from a G to A substitution at nucleotide position 965, causing the serine (S) at amino acid position 322 to be replaced by an asparagine (N). 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
0.13
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.042
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.076
N
LIST_S2
Benign
0.47
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.51
N
REVEL
Benign
0.079
Sift
Benign
0.081
T
Sift4G
Benign
0.48
T
Polyphen
0.31
B
Vest4
0.058
MutPred
0.14
Loss of phosphorylation at S322 (P = 0.0228);
MVP
0.37
MPC
1.0
ClinPred
0.15
T
GERP RS
3.6
Varity_R
0.10
gMVP
0.30

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.

Other links and lift over

dbSNP: rs1437351085; hg19: chr18-77917820; API