20-9575512-G-T

Variant names:

• chr20-9575512-G-T
• rs11087847
• NM_177990.4:c.990+4633C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

LOC105372523 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177990.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK5	NM_177990.4	MANE Select	c.990+4633C>A		intron	N/A	NP_817127.1
	PAK5	NM_020341.5		c.990+4633C>A		intron	N/A	NP_065074.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK5	ENST00000353224.10	TSL:1 MANE Select	c.990+4633C>A		intron	N/A	ENSP00000322957.5
	PAK5	ENST00000378423.5	TSL:1	c.990+4633C>A		intron	N/A	ENSP00000367679.1
	PAK5	ENST00000378429.3	TSL:1	c.990+4633C>A		intron	N/A	ENSP00000367686.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0456 AC: 1896 AN: 41540

American (AMR) AF: 0.148 AC: 2262 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3472

East Asian (EAS) AF: 0.237 AC: 1223 AN: 5166

South Asian (SAS) AF: 0.0695 AC: 335 AN: 4820

European-Finnish (FIN) AF: 0.0977 AC: 1035 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0906 AC: 6157 AN: 67990

Other (OTH) AF: 0.106 AC: 224 AN: 2114

Alfa AF: 0.0654 Hom.: 144

Bravo AF: 0.0996

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.32
PhyloP100		0.043
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: rs11087847; hg19: chr20-9556159;