X-111162977-GGAA-GGAAGAAGAA

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_002578.5(PAK3):​c.543_548dupAGAAGA​(p.Glu181_Glu182dup) variant causes a disruptive inframe insertion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,090,699 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.000013 ( 0 hom. 9 hem. )

Consequence

PAK3
NM_002578.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.19
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
BS2
High Hemizygotes in GnomAdExome4 at 9 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAK3NM_002578.5 linkc.543_548dupAGAAGA p.Glu181_Glu182dup disruptive_inframe_insertion Exon 9 of 18 ENST00000372007.10 NP_002569.1 O75914-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAK3ENST00000372007.10 linkc.543_548dupAGAAGA p.Glu181_Glu182dup disruptive_inframe_insertion Exon 9 of 18 1 NM_002578.5 ENSP00000361077.4 O75914-2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.0000128
AC:
14
AN:
1090699
Hom.:
0
Cov.:
28
AF XY:
0.0000252
AC XY:
9
AN XY:
356697
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000156
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-110406205; API