rs6056891

chr20-9798081-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177990.4(PAK5):c.-162+40681C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 151,996 control chromosomes in the GnomAD database, including 43,008 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 0.75 (43008 hom., cov: 32)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

Genes affected

PAK5 (HGNC:15916): (p21 (RAC1) activated kinase 5) The protein encoded by this gene is a member of the PAK family of Ser/Thr protein kinases. PAK family members are known to be effectors of Rac/Cdc42 GTPases, which have been implicated in the regulation of cytoskeletal dynamics, proliferation, and cell survival signaling. This kinase contains a CDC42/Rac1 interactive binding (CRIB) motif, and has been shown to bind CDC42 in the presence of GTP. This kinase is predominantly expressed in brain. It is capable of promoting neurite outgrowth, and thus may play a role in neurite development. This kinase is associated with microtubule networks and induces microtubule stabilization. The subcellular localization of this kinase is tightly regulated during cell cycle progression. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAK5	NM_177990.4	c.-162+40681C>T		intron_variant		ENST00000353224.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAK5	ENST00000353224.10	c.-162+40681C>T		intron_variant		1	NM_177990.4	P1
PAK5	ENST00000378423.5	c.-310-13575C>T		intron_variant		1		P1
PAK5	ENST00000378429.3	c.-162+20599C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113888 AN: 151878 Hom.: 42971 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.750 AC: 113979 AN: 151996 Hom.: 43008 Cov.: 32 AF XY: 0.750 AC XY: 55708 AN XY: 74264

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.744

Alfa AF: 0.720 Hom.: 55853

Bravo AF: 0.757

Asia WGS AF: 0.753 AC: 2621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.3
Dann	Benign	0.30

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: rs6056891; hg19: chr20-9778729;