Variant 20-9562975-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_177990.4(PAK5):c.1532G>A(p.Ser511Asn) variant causes a missense change. The variant allele was found at a frequency of 0.33 in 1,609,848 control chromosomes in the GnomAD database, including 100,081 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.45 ( 19330 hom., cov: 31)

Exomes 𝑓: 0.32 ( 80751 hom. )

Consequence

PAK5
NM_177990.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.26

Variant links:

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]

PAK5 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7013694E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAK5	NM_177990.4 linkuse as main transcript	c.1532G>A	p.Ser511Asn	missense_variant	6/10	ENST00000353224.10
LOC105372523	XR_937250.3 linkuse as main transcript	n.35C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PAK5	ENST00000353224.10 linkuse as main transcript	c.1532G>A	p.Ser511Asn	missense_variant	6/10	1	NM_177990.4	P1
PAK5	ENST00000378423.5 linkuse as main transcript	c.1532G>A	p.Ser511Asn	missense_variant	7/11	1		P1
PAK5	ENST00000378429.3 linkuse as main transcript	c.1532G>A	p.Ser511Asn	missense_variant	7/11	1		P1
	ENST00000657954.1 linkuse as main transcript	n.35C>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68724

AN:

151814

Hom.:

19272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.798

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.435

GnomAD3 exomes

AF:

0.372

AC:

93360

AN:

251240

Hom.:

20047

AF XY:

0.356

AC XY:

48358

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.811

Gnomad AMR exome

AF:

0.413

Gnomad ASJ exome

AF:

0.407

Gnomad EAS exome

AF:

0.574

Gnomad SAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.317

AC:

462285

AN:

1457916

Hom.:

80751

Cov.:

AF XY:

0.316

AC XY:

228925

AN XY:

725420

show subpopulations

Gnomad4 AFR exome

AF:

0.815

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.567

Gnomad4 SAS exome

AF:

0.293

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.289

Gnomad4 OTH exome

AF:

0.351

GnomAD4 genome

AF:

0.453

AC:

68843

AN:

151932

Hom.:

19330

Cov.:

AF XY:

0.452

AC XY:

33580

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.799

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.569

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.293

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.334

Hom.:

19750

Bravo

AF:

0.480

TwinsUK

AF:

0.284

AC:

1053

ALSPAC

AF:

0.284

AC:

1096

ESP6500AA

AF:

0.791

AC:

3483

ESP6500EA

AF:

0.309

AC:

2654

ExAC

AF:

0.376

AC:

45631

Asia WGS

AF:

0.473

AC:

1645

AN:

3478

EpiCase

AF:

0.300

EpiControl

AF:

0.303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.32

DEOGEN2

Benign

0.13

T;T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.023

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.55

.;.;T

MetaRNN

Benign

0.000017

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.91

P;P;P

PrimateAI

Uncertain

0.72

PROVEAN

Benign

2.2

N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.089

MPC

0.26

ClinPred

0.0077

GERP RS

5.9

Varity_R

0.42

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over