15-40250739-A-G

Position:

• chr15-40250739-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAK6	NM_001395430.1	c.-117-2439A>G		intron_variant		ENST00000560346.6
BUB1B-PAK6	NM_001128628.3	c.-117-2439A>G		intron_variant
PAK6-AS1	NR_168270.1	n.2103T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAK6	ENST00000560346.6	c.-117-2439A>G		intron_variant		5	NM_001395430.1	P1
PAK6-AS1	ENST00000623360.1	n.2054T>C		non_coding_transcript_exon_variant	2/2	2

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

Gnomad4 FIN exome AF: 0.176

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

Gnomad4 AFR AF: 0.0592

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.163

Alfa AF: 0.151 Hom.: 381

Bravo AF: 0.145

Asia WGS AF: 0.160 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.73

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: rs8035733; hg19: chr15-40542940;