rs731497

chr15-40262864-T-C

Variant summary

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

The NM_001395430.1(PAK6):c.-5-1917T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,042 control chromosomes in the GnomAD database, including 12,545 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 0.39 (12545 hom., cov: 33)
• Consequence: PAK6 NM_001395430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAK6	NM_001395430.1	c.-5-1917T>C		intron_variant		ENST00000560346.6
BUB1B-PAK6	NM_001128628.3	c.-5-1917T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAK6	ENST00000560346.6	c.-5-1917T>C		intron_variant		5	NM_001395430.1	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59804 AN: 151924 Hom.: 12514 Cov.: 33

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.394 AC: 59894 AN: 152042 Hom.: 12545 Cov.: 33 AF XY: 0.398 AC XY: 29587 AN XY: 74326

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.375

Alfa AF: 0.332 Hom.: 11329

Bravo AF: 0.394

Asia WGS AF: 0.385 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.6
Dann	Benign	0.79

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: rs731497; hg19: chr15-40555065;