15-40265067-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395430.1(PAK6):​c.204+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

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>T		intron	N/A	NP_001382359.1	Q9NQU5-1
	BUB1B-PAK6	NM_001128628.3		c.204+78C>T		intron	N/A	NP_001122100.1
	BUB1B-PAK6	NM_001128629.3		c.204+78C>T		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>T		intron	N/A	ENSP00000453858.1	Q9NQU5-1
	PAK6	ENST00000260404.8	TSL:1	c.204+78C>T		intron	N/A	ENSP00000260404.4	Q9NQU5-1
	PAK6	ENST00000542403.3	TSL:1	c.204+78C>T		intron	N/A	ENSP00000439597.2	Q9NQU5-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1178150 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 583686

African (AFR) AF: 0.00 AC: 0 AN: 26428

American (AMR) AF: 0.00 AC: 0 AN: 26598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19878

East Asian (EAS) AF: 0.00 AC: 0 AN: 35870

South Asian (SAS) AF: 0.00 AC: 0 AN: 67258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 901408

Other (OTH) AF: 0.00 AC: 0 AN: 50112

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		1.4

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;