rs8035733

Variant names:

• chr15-40250739-A-G
• rs8035733
• NM_001395430.1:c.-117-2439A>G

Variant summary

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

The NM_001395430.1(PAK6):​c.-117-2439A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,296 control chromosomes in the GnomAD database, including 2,175 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 0.16 (2174 hom., cov: 33)
  • Exomes 𝑓: 0.18 (1 hom.)
• Consequence: PAK6 NM_001395430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 5 publications found

Genes affected

PAK6 (HGNC:16061): (p21 (RAC1) activated kinase 6) This gene encodes a member of a family of p21-stimulated serine/threonine protein kinases, which contain an amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. These kinases function in a number of cellular processes, including cytoskeleton rearrangement, apoptosis, and the mitogen-activated protein (MAP) kinase signaling pathway. The protein encoded by this gene interacts with androgen receptor (AR) and translocates to the nucleus, where it is involved in transcriptional regulation. Changes in expression of this gene have been linked to prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

BUB1B-PAK6 (HGNC:52276): (BUB1B-PAK6 readthrough) This gene represents readthrough transcription between the genes BUB1B (mitotic checkpoint serine/threonine-protein kinase BUB1 beta) and PAK6 (serine/threonine-protein kinase PAK 6). The protein encoded by the readthrough transcripts is the same as the product of the downstream gene (PAK6). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

PAK6-AS1 (HGNC:33868): (PAK6 antisense RNA 1)

ENSG00000299376 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395430.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK6	NM_001395430.1	MANE Select	c.-117-2439A>G		intron	N/A	NP_001382359.1	Q9NQU5-1
	BUB1B-PAK6	NM_001128628.3		c.-117-2439A>G		intron	N/A	NP_001122100.1
	BUB1B-PAK6	NM_001128629.3		c.-117-2439A>G		intron	N/A	NP_001122101.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK6	ENST00000560346.6	TSL:5 MANE Select	c.-117-2439A>G		intron	N/A	ENSP00000453858.1	Q9NQU5-1
	PAK6	ENST00000260404.8	TSL:1	c.-117-2439A>G		intron	N/A	ENSP00000260404.4	Q9NQU5-1
	BUB1B-PAK6	ENST00000559435.1	TSL:5	n.300-2439A>G		intron	N/A	ENSP00000457109.1	H3BTB9

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23672 AN: 152144 Hom.: 2177 Cov.: 33

Gnomad AFR AF: 0.0591

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.176 AC: 6 AN: 34 Hom.: 1 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.176 AC: 6 AN: 34

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.155 AC: 23656 AN: 152262 Hom.: 2174 Cov.: 33 AF XY: 0.157 AC XY: 11669 AN XY: 74450

African (AFR) AF: 0.0592 AC: 2458 AN: 41550

American (AMR) AF: 0.145 AC: 2224 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3468

East Asian (EAS) AF: 0.106 AC: 548 AN: 5192

South Asian (SAS) AF: 0.254 AC: 1225 AN: 4830

European-Finnish (FIN) AF: 0.177 AC: 1877 AN: 10606

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13816 AN: 67996

Other (OTH) AF: 0.163 AC: 345 AN: 2112

Alfa AF: 0.142 Hom.: 1155

Bravo AF: 0.145

Asia WGS AF: 0.160 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.73
PhyloP100		0.26
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: rs8035733; hg19: chr15-40542940;