rs4799144

Positions:

• chr18-80199442-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032510.4(PARD6G):​c.295+3268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 152,162 control chromosomes in the GnomAD database, including 633 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.076 (633 hom., cov: 33)
• Consequence: PARD6G NM_032510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD6G	NM_032510.4	c.295+3268C>T		intron_variant		ENST00000353265.8	NP_115899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD6G	ENST00000353265.8	c.295+3268C>T		intron_variant		1	NM_032510.4	ENSP00000343144	P1
PARD6G	ENST00000470488.2	c.295+3268C>T		intron_variant		1		ENSP00000468735
	ENST00000588950.1	n.1646+1804G>A		intron_variant, non_coding_transcript_variant		2
PARD6G	ENST00000463384.1	c.*41+2522C>T		intron_variant		3		ENSP00000466076

Frequencies

GnomAD3 genomes AF: 0.0756 AC: 11489 AN: 152044 Hom.: 628 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0228

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0480

Gnomad OTH AF: 0.0760

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0756 AC: 11509 AN: 152162 Hom.: 633 Cov.: 33 AF XY: 0.0723 AC XY: 5381 AN XY: 74388

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0228

Gnomad4 NFE AF: 0.0480

Gnomad4 OTH AF: 0.0771

Alfa AF: 0.0632 Hom.: 78

Bravo AF: 0.0829

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.58
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs4799144; hg19: chr18-77957325;