rs731497

Variant names:

• chr15-40262864-T-C
• rs731497
• NM_001395430.1:c.-5-1917T>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.-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
• Publications: 5 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=-0.89).
• 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 rank	MANE	Protein	UniProt
PAK6	NM_001395430.1	c.-5-1917T>C		intron_variant	Intron 3 of 10	ENST00000560346.6	NP_001382359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK6	ENST00000560346.6	c.-5-1917T>C		intron_variant	Intron 3 of 10	5	NM_001395430.1	ENSP00000453858.1
BUB1B-PAK6	ENST00000559435.1	n.412-1579T>C		intron_variant	Intron 4 of 5	5		ENSP00000457109.1

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

African (AFR) AF: 0.522 AC: 21615 AN: 41428

American (AMR) AF: 0.415 AC: 6352 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 779 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1391 AN: 5180

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4814

European-Finnish (FIN) AF: 0.445 AC: 4705 AN: 10564

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21824 AN: 67976

Other (OTH) AF: 0.375 AC: 792 AN: 2110

Alfa AF: 0.339 Hom.: 14944

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
PhyloP100		0.35
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: rs731497; hg19: chr15-40555065;