20-9544431-A-G
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_177990.4(PAK5):āc.1807T>Cā(p.Leu603Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,613,890 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0081 ( 13 hom., cov: 32)
Exomes š: 0.00090 ( 18 hom. )
Consequence
PAK5
NM_177990.4 synonymous
NM_177990.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.16
Genes affected
PAK5 (HGNC:15916): (p21 (RAC1) activated kinase 5) The protein encoded by this gene is a member of the PAK family of Ser/Thr protein kinases. PAK family members are known to be effectors of Rac/Cdc42 GTPases, which have been implicated in the regulation of cytoskeletal dynamics, proliferation, and cell survival signaling. This kinase contains a CDC42/Rac1 interactive binding (CRIB) motif, and has been shown to bind CDC42 in the presence of GTP. This kinase is predominantly expressed in brain. It is capable of promoting neurite outgrowth, and thus may play a role in neurite development. This kinase is associated with microtubule networks and induces microtubule stabilization. The subcellular localization of this kinase is tightly regulated during cell cycle progression. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 20-9544431-A-G is Benign according to our data. Variant chr20-9544431-A-G is described in ClinVar as [Benign]. Clinvar id is 786363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.16 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00809 (1233/152338) while in subpopulation AFR AF= 0.027 (1124/41568). AF 95% confidence interval is 0.0257. There are 13 homozygotes in gnomad4. There are 604 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1233 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAK5 | NM_177990.4 | c.1807T>C | p.Leu603Leu | synonymous_variant | 8/10 | ENST00000353224.10 | NP_817127.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAK5 | ENST00000353224.10 | c.1807T>C | p.Leu603Leu | synonymous_variant | 8/10 | 1 | NM_177990.4 | ENSP00000322957.5 | ||
PAK5 | ENST00000378423.5 | c.1807T>C | p.Leu603Leu | synonymous_variant | 9/11 | 1 | ENSP00000367679.1 | |||
PAK5 | ENST00000378429.3 | c.1807T>C | p.Leu603Leu | synonymous_variant | 9/11 | 1 | ENSP00000367686.3 |
Frequencies
GnomAD3 genomes AF: 0.00807 AC: 1229AN: 152220Hom.: 13 Cov.: 32
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GnomAD3 exomes AF: 0.00207 AC: 521AN: 251460Hom.: 9 AF XY: 0.00154 AC XY: 209AN XY: 135906
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GnomAD4 exome AF: 0.000898 AC: 1312AN: 1461552Hom.: 18 Cov.: 30 AF XY: 0.000780 AC XY: 567AN XY: 727130
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GnomAD4 genome AF: 0.00809 AC: 1233AN: 152338Hom.: 13 Cov.: 32 AF XY: 0.00811 AC XY: 604AN XY: 74498
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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 | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 15, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
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CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at