18-80160078-C-A

Position:

• chr18-80160078-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032510.4(PARD6G):​c.824G>T​(p.Gly275Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: PARD6G NM_032510.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.94

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-AS1 (HGNC:):

ACMG classification

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=0.14701465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD6G	NM_032510.4	c.824G>T	p.Gly275Val	missense_variant	3/3	ENST00000353265.8	NP_115899.1
PARD6G-AS1	NR_028339.1	n.332-2438C>A		intron_variant
PARD6G-AS1	NR_028340.1	n.331+11824C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD6G	ENST00000353265.8	c.824G>T	p.Gly275Val	missense_variant	3/3	1	NM_032510.4	ENSP00000343144.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.824G>T (p.G275V) alteration is located in exon 3 (coding exon 3) of the PARD6G gene. This alteration results from a G to T substitution at nucleotide position 824, causing the glycine (G) at amino acid position 275 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	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Uncertain	0.022	D
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.071
MutPred		0.27		Loss of glycosylation at T273 (P = 0.13);
MVP		0.49
MPC		1.1
ClinPred		0.69	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.19
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-77917961;