18-80217100-C-A

Variant names:

• chr18-80217100-C-A
• rs6506816
• NM_032510.4:c.73-14168G>T

Variant summary

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

The NM_032510.4(PARD6G):​c.73-14168G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,122 control chromosomes in the GnomAD database, including 55,389 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 0.85 (55389 hom., cov: 31)
• Consequence: PARD6G NM_032510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD6G	NM_032510.4	c.73-14168G>T		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.73-14168G>T		intron_variant	Intron 1 of 2	1	NM_032510.4	ENSP00000343144.3
PARD6G	ENST00000470488.2	c.73-14168G>T		intron_variant	Intron 1 of 2	1		ENSP00000468735.1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129564 AN: 152004 Hom.: 55347 Cov.: 31

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.852 AC: 129661 AN: 152122 Hom.: 55389 Cov.: 31 AF XY: 0.849 AC XY: 63141 AN XY: 74346

African (AFR) AF: 0.833 AC: 34547 AN: 41496

American (AMR) AF: 0.865 AC: 13220 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2991 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3329 AN: 5158

South Asian (SAS) AF: 0.796 AC: 3835 AN: 4816

European-Finnish (FIN) AF: 0.861 AC: 9107 AN: 10576

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59889 AN: 68008

Other (OTH) AF: 0.852 AC: 1801 AN: 2114

Alfa AF: 0.873 Hom.: 96194

Bravo AF: 0.849

Asia WGS AF: 0.777 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.41
PhyloP100		-0.94
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: rs6506816; hg19: chr18-77974983;