Variant 20-9565907-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_177990.4(PAK5):c.1468C>T(p.Leu490=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0559 in 1,612,356 control chromosomes in the GnomAD database, including 3,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 372 hom., cov: 32)

Exomes 𝑓: 0.056 ( 3563 hom. )

Consequence

PAK5
NM_177990.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.81

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 20-9565907-G-A is Benign according to our data. Variant chr20-9565907-G-A is described in ClinVar as [Benign]. Clinvar id is 1676927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 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.1468C>T	p.Leu490=	synonymous_variant	5/10	ENST00000353224.10
LOC105372523	XR_937250.3 linkuse as main transcript	n.161+2806G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PAK5	ENST00000353224.10 linkuse as main transcript	c.1468C>T	p.Leu490=	synonymous_variant	5/10	1	NM_177990.4	P1
PAK5	ENST00000378423.5 linkuse as main transcript	c.1468C>T	p.Leu490=	synonymous_variant	6/11	1		P1
PAK5	ENST00000378429.3 linkuse as main transcript	c.1468C>T	p.Leu490=	synonymous_variant	6/11	1		P1
	ENST00000657954.1 linkuse as main transcript	n.161+2806G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0523

AC:

7948

AN:

151950

Hom.:

369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0272

Gnomad AMI

AF:

0.0408

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.0627

Gnomad FIN

AF:

0.0655

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0535

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0641

AC:

16052

AN:

250370

Hom.:

1081

AF XY:

0.0645

AC XY:

8729

AN XY:

135274

show subpopulations

Gnomad AFR exome

AF:

0.0265

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.0578

Gnomad EAS exome

AF:

0.285

Gnomad SAS exome

AF:

0.0533

Gnomad FIN exome

AF:

0.0652

Gnomad NFE exome

AF:

0.0519

Gnomad OTH exome

AF:

0.0526

GnomAD4 exome

AF:

0.0563

AC:

82253

AN:

1460288

Hom.:

3563

Cov.:

AF XY:

0.0562

AC XY:

40852

AN XY:

726448

show subpopulations

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.0177

Gnomad4 ASJ exome

AF:

0.0587

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.0516

Gnomad4 FIN exome

AF:

0.0643

Gnomad4 NFE exome

AF:

0.0509

Gnomad4 OTH exome

AF:

0.0600

GnomAD4 genome

AF:

0.0523

AC:

7947

AN:

152068

Hom.:

372

Cov.:

AF XY:

0.0540

AC XY:

4016

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0271

Gnomad4 AMR

AF:

0.0277

Gnomad4 ASJ

AF:

0.0571

Gnomad4 EAS

AF:

0.278

Gnomad4 SAS

AF:

0.0624

Gnomad4 FIN

AF:

0.0655

Gnomad4 NFE

AF:

0.0534

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0522

Hom.:

623

Bravo

AF:

0.0486

Asia WGS

AF:

0.148

AC:

514

AN:

3478

EpiCase

AF:

0.0485

EpiControl

AF:

0.0473

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2022	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.4

DANN

Benign

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over