X-111123532-A-T

Position:

• chrX-111123532-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002578.5(PAK3):​c.175+254A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0742 in 112,450 control chromosomes in the GnomAD database, including 528 homozygotes. There are 2,202 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.074 (528 hom., 2202 hem., cov: 23)
• Consequence: PAK3 NM_002578.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.175

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-111123532-A-T is Benign according to our data. Variant chrX-111123532-A-T is described in ClinVar as [Benign]. Clinvar id is 1181161.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAK3	NM_002578.5	c.175+254A>T		intron_variant		ENST00000372007.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAK3	ENST00000372007.10	c.175+254A>T		intron_variant		1	NM_002578.5	P1

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 8315 AN: 112397 Hom.: 528 Cov.: 23 AF XY: 0.0629 AC XY: 2174 AN XY: 34571

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.0549

Gnomad NFE AF: 0.0242

Gnomad OTH AF: 0.0668

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

GnomAD4 genome AF: 0.0742 AC: 8341 AN: 112450 Hom.: 528 Cov.: 23 AF XY: 0.0636 AC XY: 2202 AN XY: 34634

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0242

Gnomad4 OTH AF: 0.0659

Alfa AF: 0.0501 Hom.: 251

Bravo AF: 0.0819

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.85
CADD	Benign	2.7
DANN	Benign	0.66

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: rs7879757; hg19: chrX-110366760;