rs936216

Variant names:

• chr15-40265067-C-A
• rs936216
• NM_001395430.1:c.204+78C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-40265067-C-A
• chr15-40265067-C-G
• chr15-40265067-C-T

Variant summary

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

The NM_001395430.1(PAK6):​c.204+78C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,328,168 control chromosomes in the GnomAD database, including 367,886 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 0.70 (37308 hom., cov: 31)
  • Exomes 𝑓: 0.75 (330578 hom.)
• Consequence: PAK6 NM_001395430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 8 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]

ENSG00000299376 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 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.204+78C>A		intron	N/A	NP_001382359.1	Q9NQU5-1
	BUB1B-PAK6	NM_001128628.3		c.204+78C>A		intron	N/A	NP_001122100.1
	BUB1B-PAK6	NM_001128629.3		c.204+78C>A		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.204+78C>A		intron	N/A	ENSP00000453858.1	Q9NQU5-1
	PAK6	ENST00000260404.8	TSL:1	c.204+78C>A		intron	N/A	ENSP00000260404.4	Q9NQU5-1
	PAK6	ENST00000542403.3	TSL:1	c.204+78C>A		intron	N/A	ENSP00000439597.2	Q9NQU5-1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105617 AN: 151812 Hom.: 37290 Cov.: 31

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.713

GnomAD4 exome AF: 0.747 AC: 879059 AN: 1176238 Hom.: 330578 AF XY: 0.744 AC XY: 433779 AN XY: 582724

African (AFR) AF: 0.584 AC: 15414 AN: 26384

American (AMR) AF: 0.603 AC: 16017 AN: 26554

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 16332 AN: 19856

East Asian (EAS) AF: 0.798 AC: 28602 AN: 35862

South Asian (SAS) AF: 0.635 AC: 42640 AN: 67182

European-Finnish (FIN) AF: 0.715 AC: 33569 AN: 46920

Middle Eastern (MID) AF: 0.686 AC: 2508 AN: 3654

European-Non Finnish (NFE) AF: 0.763 AC: 686471 AN: 899782

Other (OTH) AF: 0.749 AC: 37506 AN: 50044

GnomAD4 genome AF: 0.696 AC: 105681 AN: 151930 Hom.: 37308 Cov.: 31 AF XY: 0.692 AC XY: 51412 AN XY: 74264

African (AFR) AF: 0.589 AC: 24383 AN: 41404

American (AMR) AF: 0.647 AC: 9884 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2849 AN: 3468

East Asian (EAS) AF: 0.819 AC: 4224 AN: 5160

South Asian (SAS) AF: 0.634 AC: 3052 AN: 4814

European-Finnish (FIN) AF: 0.720 AC: 7595 AN: 10548

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51337 AN: 67942

Other (OTH) AF: 0.714 AC: 1507 AN: 2110

Alfa AF: 0.740 Hom.: 69076

Bravo AF: 0.689

Asia WGS AF: 0.692 AC: 2407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		1.4
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: rs936216; hg19: chr15-40557268;