rs16970458

Variant names:

• chr15-40242778-T-C
• rs16970458
• NM_001395430.1:c.-118+2097T>C

Variant summary

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

The NM_001395430.1(PAK6):​c.-118+2097T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,022 control chromosomes in the GnomAD database, including 25,358 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 0.56 (25358 hom., cov: 32)
• Consequence: PAK6 NM_001395430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK6	NM_001395430.1	MANE Select	c.-118+2097T>C		intron	N/A	NP_001382359.1
	BUB1B-PAK6	NM_001128628.3		c.-118+2097T>C		intron	N/A	NP_001122100.1
	BUB1B-PAK6	NM_001128629.3		c.-117-10400T>C		intron	N/A	NP_001122101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK6	ENST00000560346.6	TSL:5 MANE Select	c.-118+2097T>C		intron	N/A	ENSP00000453858.1
	PAK6	ENST00000260404.8	TSL:1	c.-118+2097T>C		intron	N/A	ENSP00000260404.4
	BUB1B-PAK6	ENST00000559435.1	TSL:5	n.299+2097T>C		intron	N/A	ENSP00000457109.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84411 AN: 151902 Hom.: 25357 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.555 AC: 84414 AN: 152022 Hom.: 25358 Cov.: 32 AF XY: 0.549 AC XY: 40819 AN XY: 74318

African (AFR) AF: 0.356 AC: 14752 AN: 41446

American (AMR) AF: 0.493 AC: 7529 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2598 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1300 AN: 5160

South Asian (SAS) AF: 0.511 AC: 2464 AN: 4824

European-Finnish (FIN) AF: 0.630 AC: 6658 AN: 10564

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47061 AN: 67962

Other (OTH) AF: 0.579 AC: 1218 AN: 2104

Alfa AF: 0.634 Hom.: 54511

Bravo AF: 0.534

Asia WGS AF: 0.379 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.028
DANN	Benign	0.66
PhyloP100		-2.3
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: rs16970458; hg19: chr15-40534979;