NM_177990.4:c.-161-42687A>G

Variant names:

• chr20-9754122-T-C
• rs2423462
• NM_177990.4:c.-161-42687A>G

Variant summary

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

The NM_177990.4(PAK5):​c.-161-42687A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,056 control chromosomes in the GnomAD database, including 21,103 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 0.52 (21103 hom., cov: 33)
• Consequence: PAK5 NM_177990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK5	NM_177990.4	c.-161-42687A>G		intron_variant	Intron 1 of 9	ENST00000353224.10	NP_817127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK5	ENST00000353224.10	c.-161-42687A>G		intron_variant	Intron 1 of 9	1	NM_177990.4	ENSP00000322957.5
PAK5	ENST00000378423.5	c.-162+30236A>G		intron_variant	Intron 2 of 10	1		ENSP00000367679.1
PAK5	ENST00000378429.3	c.-161-42687A>G		intron_variant	Intron 2 of 10	1		ENSP00000367686.3

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79645 AN: 151938 Hom.: 21070 Cov.: 33

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.524 AC: 79729 AN: 152056 Hom.: 21103 Cov.: 33 AF XY: 0.532 AC XY: 39563 AN XY: 74326

African (AFR) AF: 0.513 AC: 21263 AN: 41470

American (AMR) AF: 0.633 AC: 9659 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3472

East Asian (EAS) AF: 0.611 AC: 3156 AN: 5164

South Asian (SAS) AF: 0.548 AC: 2647 AN: 4826

European-Finnish (FIN) AF: 0.581 AC: 6154 AN: 10592

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33419 AN: 67960

Other (OTH) AF: 0.517 AC: 1091 AN: 2110

Alfa AF: 0.507 Hom.: 60654

Bravo AF: 0.530

Asia WGS AF: 0.585 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.72
DANN	Benign	0.41
PhyloP100		-0.42
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: rs2423462; hg19: chr20-9734770;