rs742450

Positions:

• chr20-9755845-C-T

Variant summary

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

The NM_177990.4(PAK5):​c.-161-44410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,156 control chromosomes in the GnomAD database, including 2,249 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 0.16 (2249 hom., cov: 33)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK5	NM_177990.4	c.-161-44410G>A		intron_variant		ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.-161-44410G>A		intron_variant		1	NM_177990.4	ENSP00000322957	P1
PAK5	ENST00000378423.5	c.-162+28513G>A		intron_variant		1		ENSP00000367679	P1
PAK5	ENST00000378429.3	c.-161-44410G>A		intron_variant		1		ENSP00000367686	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24665 AN: 152038 Hom.: 2249 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.162 AC: 24657 AN: 152156 Hom.: 2249 Cov.: 33 AF XY: 0.159 AC XY: 11805 AN XY: 74392

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.181

Alfa AF: 0.174 Hom.: 472

Bravo AF: 0.162

Asia WGS AF: 0.189 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.7
DANN	Benign	0.42

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: rs742450; hg19: chr20-9736493;