rs10521534

chrX-111178213-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002578.5(PAK3):c.830+5132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 110,677 control chromosomes in the GnomAD database, including 2,557 homozygotes. There are 4,493 hemizygotes in GnomAD. 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 0.15 (2557 hom., 4493 hem., cov: 22)
• Consequence: PAK3 NM_002578.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAK3	NM_002578.5	c.830+5132A>G		intron_variant		ENST00000372007.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAK3	ENST00000372007.10	c.830+5132A>G		intron_variant		1	NM_002578.5	P1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 16557 AN: 110622 Hom.: 2555 Cov.: 22 AF XY: 0.135 AC XY: 4465 AN XY: 32984

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.00293

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.0114

Gnomad EAS AF: 0.00113

Gnomad SAS AF: 0.0272

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.150 AC: 16594 AN: 110677 Hom.: 2557 Cov.: 22 AF XY: 0.136 AC XY: 4493 AN XY: 33049

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.0814

Gnomad4 ASJ AF: 0.0114

Gnomad4 EAS AF: 0.00113

Gnomad4 SAS AF: 0.0265

Gnomad4 FIN AF: 0.0117

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.126

Alfa AF: 0.107 Hom.: 893

Bravo AF: 0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.2
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs10521534; hg19: chrX-110421441;