20-9544954-T-C

Position:

• chr20-9544954-T-C

Variant summary

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

The NM_177990.4(PAK5):​c.1744-460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,064 control chromosomes in the GnomAD database, including 19,424 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 0.45 (19424 hom., cov: 32)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK5	NM_177990.4	c.1744-460A>G		intron_variant		ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.1744-460A>G		intron_variant		1	NM_177990.4	ENSP00000322957	P1
PAK5	ENST00000378423.5	c.1744-460A>G		intron_variant		1		ENSP00000367679	P1
PAK5	ENST00000378429.3	c.1744-460A>G		intron_variant		1		ENSP00000367686	P1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69068 AN: 151948 Hom.: 19366 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.455 AC: 69185 AN: 152064 Hom.: 19424 Cov.: 32 AF XY: 0.454 AC XY: 33750 AN XY: 74334

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.440

Alfa AF: 0.318 Hom.: 10544

Bravo AF: 0.481

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.49
DANN	Benign	0.53

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: rs2072952; hg19: chr20-9525601;