20-9575512-G-T

Position:

• chr20-9575512-G-T

Variant summary

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

The NM_177990.4(PAK5):​c.990+4633C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 152,186 control chromosomes in the GnomAD database, including 755 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 0.089 (755 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAK5	NM_177990.4	c.990+4633C>A		intron_variant		ENST00000353224.10
LOC105372523	XR_937250.3	n.591+4204G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAK5	ENST00000353224.10	c.990+4633C>A		intron_variant		1	NM_177990.4	P1
PAK5	ENST00000378423.5	c.990+4633C>A		intron_variant		1		P1
PAK5	ENST00000378429.3	c.990+4633C>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 13585 AN: 152068 Hom.: 749 Cov.: 32

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.106

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0894 AC: 13600 AN: 152186 Hom.: 755 Cov.: 32 AF XY: 0.0904 AC XY: 6727 AN XY: 74394

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.0695

Gnomad4 FIN AF: 0.0977

Gnomad4 NFE AF: 0.0906

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0657 Hom.: 140

Bravo AF: 0.0996

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.32

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: rs11087847; hg19: chr20-9556159;