Genetic Variant NM_001395430.1:c.204+78C>A (chr15-40265067-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Variant links:

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]

PAK6 links:

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]

BUB1B-PAK6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK6	NM_001395430.1 link	c.204+78C>A		intron_variant	Intron 4 of 10	ENST00000560346.6	NP_001382359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK6	ENST00000560346.6 link	c.204+78C>A		intron_variant	Intron 4 of 10	5	NM_001395430.1	ENSP00000453858.1		Q9NQU5-1
BUB1B-PAK6	ENST00000559435.1 link	n.*361C>A		downstream_gene_variant		5		ENSP00000457109.1		H3BTB9

Frequencies

GnomAD3 genomes

AF:

0.696

AC:

105617

AN:

151812

Hom.:

37290

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.584

Gnomad4 AMR exome

AF:

0.603

Gnomad4 ASJ exome

AF:

0.823

Gnomad4 EAS exome

AF:

0.798

Gnomad4 SAS exome

AF:

0.635

Gnomad4 FIN exome

AF:

0.715

Gnomad4 NFE exome

AF:

0.763

Gnomad4 OTH exome

AF:

0.749

GnomAD4 genome

AF:

0.696

AC:

105681

AN:

151930

Hom.:

37308

Cov.:

AF XY:

0.692

AC XY:

51412

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.589

Gnomad4 AMR

AF:

0.647

Gnomad4 ASJ

AF:

0.822

Gnomad4 EAS

AF:

0.819

Gnomad4 SAS

AF:

0.634

Gnomad4 FIN

AF:

0.720

Gnomad4 NFE

AF:

0.756

Gnomad4 OTH

AF:

0.714

Alfa

AF:

0.747

Hom.:

55027

Bravo

AF:

0.689

Asia WGS

AF:

0.692

AC:

2407

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over