rs16970458

Positions:

• chr15-40242778-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.-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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK6	NM_001395430.1	c.-118+2097T>C		intron_variant		ENST00000560346.6	NP_001382359.1
BUB1B-PAK6	NM_001128628.3	c.-118+2097T>C		intron_variant			NP_001122100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK6	ENST00000560346.6	c.-118+2097T>C		intron_variant		5	NM_001395430.1	ENSP00000453858	P1

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

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.579

Alfa AF: 0.656 Hom.: 31997

Bravo AF: 0.534

Asia WGS AF: 0.379 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.028
DANN	Benign	0.66

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: rs16970458; hg19: chr15-40534979;