20-9755715-G-C

Variant names:

• chr20-9755715-G-C
• rs742452
• NM_177990.4:c.-161-44280C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020341.5(PAK5):​c.-161-44280C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,164 control chromosomes in the GnomAD database, including 2,681 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 0.18 (2681 hom., cov: 33)
• Consequence: PAK5 NM_020341.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020341.5. 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
	PAK5	NM_177990.4	MANE Select	c.-161-44280C>G		intron	N/A	NP_817127.1
	PAK5	NM_020341.5		c.-161-44280C>G		intron	N/A	NP_065074.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK5	ENST00000353224.10	TSL:1 MANE Select	c.-161-44280C>G		intron	N/A	ENSP00000322957.5
	PAK5	ENST00000378423.5	TSL:1	c.-162+28643C>G		intron	N/A	ENSP00000367679.1
	PAK5	ENST00000378429.3	TSL:1	c.-161-44280C>G		intron	N/A	ENSP00000367686.3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26770 AN: 152046 Hom.: 2681 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.176 AC: 26761 AN: 152164 Hom.: 2681 Cov.: 33 AF XY: 0.173 AC XY: 12835 AN XY: 74380

African (AFR) AF: 0.105 AC: 4355 AN: 41542

American (AMR) AF: 0.151 AC: 2307 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1449 AN: 5168

South Asian (SAS) AF: 0.161 AC: 778 AN: 4826

European-Finnish (FIN) AF: 0.153 AC: 1616 AN: 10586

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14701 AN: 67976

Other (OTH) AF: 0.192 AC: 406 AN: 2116

Alfa AF: 0.186 Hom.: 324

Bravo AF: 0.174

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.43
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: rs742452; hg19: chr20-9736363;