rs146801179
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_002578.5(PAK3):āc.483A>Gā(p.Ala161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,205,216 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 110 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00057 ( 0 hom., 17 hem., cov: 23)
Exomes š: 0.00027 ( 0 hom. 93 hem. )
Consequence
PAK3
NM_002578.5 synonymous
NM_002578.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.552
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant X-111162929-A-G is Benign according to our data. Variant chrX-111162929-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 367714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111162929-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.552 with no splicing effect.
BS2
?
High Hemizygotes in GnomAd4 at 17 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAK3 | NM_002578.5 | c.483A>G | p.Ala161= | synonymous_variant | 9/18 | ENST00000372007.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAK3 | ENST00000372007.10 | c.483A>G | p.Ala161= | synonymous_variant | 9/18 | 1 | NM_002578.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000574 AC: 64AN: 111491Hom.: 0 Cov.: 23 AF XY: 0.000505 AC XY: 17AN XY: 33671
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GnomAD3 exomes AF: 0.000375 AC: 68AN: 181171Hom.: 0 AF XY: 0.000358 AC XY: 24AN XY: 67125
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GnomAD4 exome AF: 0.000266 AC: 291AN: 1093672Hom.: 0 Cov.: 28 AF XY: 0.000259 AC XY: 93AN XY: 359396
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GnomAD4 genome ? AF: 0.000574 AC: 64AN: 111544Hom.: 0 Cov.: 23 AF XY: 0.000504 AC XY: 17AN XY: 33734
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | PAK3: BP4, BP7, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 17, 2017 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
PAK3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Intellectual disability, X-linked 30 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at