Variant rs10521535 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000372007.10(PAK3):c.1545+41C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 1,071,314 control chromosomes in the GnomAD database, including 809 homozygotes. There are 9,591 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 303 hom., 1791 hem., cov: 23)

Exomes 𝑓: 0.029 ( 506 hom. 7800 hem. )

Consequence

PAK3
ENST00000372007.10 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.132

Variant links:

Genes affected

PAK3 (HGNC:8592): (p21 (RAC1) activated kinase 3) The protein encoded by this gene is a serine-threonine kinase and forms an activated complex with GTP-bound RAS-like (P21), CDC2 and RAC1. This protein may be necessary for dendritic development and for the rapid cytoskeletal reorganization in dendritic spines associated with synaptic plasticity. Defects in this gene are the cause of a non-syndromic form of X-linked intellectual disability. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2017]

PAK3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-111216599-C-G is Benign according to our data. Variant chrX-111216599-C-G is described in ClinVar as [Benign]. Clinvar id is 1244665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK3	NM_002578.5 linkuse as main transcript	c.1545+41C>G		intron_variant		ENST00000372007.10	NP_002569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK3	ENST00000372007.10 linkuse as main transcript	c.1545+41C>G		intron_variant		1	NM_002578.5	ENSP00000361077	P1	O75914-2

Frequencies

GnomAD3 genomes

AF:

0.0602

AC:

6706

AN:

111351

Hom.:

303

Cov.:

AF XY:

0.0528

AC XY:

1771

AN XY:

33567

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.00582

Gnomad AMR

AF:

0.0345

Gnomad ASJ

AF:

0.0129

Gnomad EAS

AF:

0.00112

Gnomad SAS

AF:

0.0177

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.0921

Gnomad NFE

AF:

0.0278

Gnomad OTH

AF:

0.0662

GnomAD3 exomes

AF:

0.0312

AC:

5691

AN:

182268

Hom.:

152

AF XY:

0.0273

AC XY:

1828

AN XY:

66902

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.0226

Gnomad ASJ exome

AF:

0.0181

Gnomad EAS exome

AF:

0.000579

Gnomad SAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.0149

Gnomad NFE exome

AF:

0.0276

Gnomad OTH exome

AF:

0.0364

GnomAD4 exome

AF:

0.0295

AC:

28303

AN:

959913

Hom.:

506

Cov.:

AF XY:

0.0296

AC XY:

7800

AN XY:

263197

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.0248

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.000474

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0283

Gnomad4 OTH exome

AF:

0.0357

GnomAD4 genome

AF:

0.0604

AC:

6727

AN:

111401

Hom.:

303

Cov.:

AF XY:

0.0533

AC XY:

1791

AN XY:

33627

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0344

Gnomad4 ASJ

AF:

0.0129

Gnomad4 EAS

AF:

0.00113

Gnomad4 SAS

AF:

0.0177

Gnomad4 FIN

AF:

0.0117

Gnomad4 NFE

AF:

0.0279

Gnomad4 OTH

AF:

0.0647

Alfa

AF:

0.0409

Hom.:

298

Bravo

AF:

0.0667

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.29

DANN

Benign

0.54

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