chr20-9663558-C-A

Variant names:

• chr20-9663558-C-A
• rs17408919
• NM_177990.4:c.-11-19219G>T

Variant summary

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

The NM_177990.4(PAK5):​c.-11-19219G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,032 control chromosomes in the GnomAD database, including 3,011 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 0.19 (3011 hom., cov: 32)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK5	NM_177990.4	c.-11-19219G>T		intron_variant	Intron 2 of 9	ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.-11-19219G>T		intron_variant	Intron 2 of 9	1	NM_177990.4	ENSP00000322957.5
PAK5	ENST00000378423.5	c.-11-19219G>T		intron_variant	Intron 3 of 10	1		ENSP00000367679.1
PAK5	ENST00000378429.3	c.-11-19219G>T		intron_variant	Intron 3 of 10	1		ENSP00000367686.3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29485 AN: 151914 Hom.: 3008 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0445

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.194 AC: 29492 AN: 152032 Hom.: 3011 Cov.: 32 AF XY: 0.189 AC XY: 14011 AN XY: 74302

African (AFR) AF: 0.168 AC: 6964 AN: 41474

American (AMR) AF: 0.164 AC: 2505 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3466

East Asian (EAS) AF: 0.0441 AC: 228 AN: 5174

South Asian (SAS) AF: 0.122 AC: 589 AN: 4824

European-Finnish (FIN) AF: 0.183 AC: 1931 AN: 10566

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15679 AN: 67934

Other (OTH) AF: 0.203 AC: 429 AN: 2110

Alfa AF: 0.224 Hom.: 6292

Bravo AF: 0.192

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.37
PhyloP100		-0.079
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: rs17408919; hg19: chr20-9644206;