18-80206083-G-C

Variant names:

• chr18-80206083-G-C
• rs4798947
• NM_032510.4:c.73-3151C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032510.4(PARD6G):​c.73-3151C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,058 control chromosomes in the GnomAD database, including 3,540 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 0.19 (3540 hom., cov: 32)
• Consequence: PARD6G NM_032510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD6G	NM_032510.4	c.73-3151C>G		intron_variant	Intron 1 of 2	ENST00000353265.8	NP_115899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD6G	ENST00000353265.8	c.73-3151C>G		intron_variant	Intron 1 of 2	1	NM_032510.4	ENSP00000343144.3
PARD6G	ENST00000470488.2	c.73-3151C>G		intron_variant	Intron 1 of 2	1		ENSP00000468735.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29445 AN: 151940 Hom.: 3529 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0686

Gnomad SAS AF: 0.0823

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.194 AC: 29478 AN: 152058 Hom.: 3540 Cov.: 32 AF XY: 0.188 AC XY: 13946 AN XY: 74330

African (AFR) AF: 0.338 AC: 13993 AN: 41440

American (AMR) AF: 0.152 AC: 2326 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 806 AN: 3466

East Asian (EAS) AF: 0.0687 AC: 356 AN: 5180

South Asian (SAS) AF: 0.0817 AC: 394 AN: 4822

European-Finnish (FIN) AF: 0.0982 AC: 1037 AN: 10564

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9981 AN: 67996

Other (OTH) AF: 0.195 AC: 411 AN: 2108

Alfa AF: 0.0612 Hom.: 54

Bravo AF: 0.206

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.65
PhyloP100		-0.083
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4798947; hg19: chr18-77963966;