rs9967942

Positions:

• chr20-9575134-A-C

Variant summary

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

The NM_177990.4(PAK5):​c.990+5011T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,044 control chromosomes in the GnomAD database, including 6,990 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 0.30 (6990 hom., cov: 32)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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]

LOC105372523 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAK5	NM_177990.4	c.990+5011T>G		intron_variant		ENST00000353224.10
LOC105372523	XR_937250.3	n.591+3826A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAK5	ENST00000353224.10	c.990+5011T>G		intron_variant		1	NM_177990.4	P1
PAK5	ENST00000378423.5	c.990+5011T>G		intron_variant		1		P1
PAK5	ENST00000378429.3	c.990+5011T>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45056 AN: 151926 Hom.: 6970 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.297 AC: 45133 AN: 152044 Hom.: 6990 Cov.: 32 AF XY: 0.295 AC XY: 21954 AN XY: 74340

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.304

Alfa AF: 0.272 Hom.: 11889

Bravo AF: 0.312

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
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: rs9967942; hg19: chr20-9555781;