rs2277562

Positions:

• chr15-40249998-C-T

Variant summary

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

The NM_001395430.1(PAK6):​c.-117-3180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,290 control chromosomes in the GnomAD database, including 2,093 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 0.15 (2093 hom., cov: 33)
• Consequence: PAK6 NM_001395430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.862

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK6	NM_001395430.1	c.-117-3180C>T		intron_variant		ENST00000560346.6	NP_001382359.1
BUB1B-PAK6	NM_001128628.3	c.-117-3180C>T		intron_variant			NP_001122100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK6	ENST00000560346.6	c.-117-3180C>T		intron_variant		5	NM_001395430.1	ENSP00000453858	P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22592 AN: 152172 Hom.: 2096 Cov.: 33

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.148 AC: 22573 AN: 152290 Hom.: 2093 Cov.: 33 AF XY: 0.149 AC XY: 11118 AN XY: 74464

Gnomad4 AFR AF: 0.0411

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.154

Alfa AF: 0.193 Hom.: 4025

Bravo AF: 0.137

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Benign	0.80

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: rs2277562; hg19: chr15-40542199;