rs16986385

Variant names:

• chrX-111152384-A-C
• rs16986385
• NM_002578.5:c.431-26A>C

Your query was ambiguous. Multiple possible variants found:

• chrX-111152384-A-C
• chrX-111152384-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002578.5(PAK3):​c.431-26A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 982,442 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000010 (0 hom. 0 hem.)
• Consequence: PAK3 NM_002578.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771
• Publications: 3 publications found

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]

PAK3 Gene-Disease associations (from GenCC):

• corpus callosum, agenesis of

  Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
• intellectual disability, X-linked 30

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK3	NM_002578.5	c.431-26A>C		intron_variant	Intron 7 of 17	ENST00000372007.10	NP_002569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK3	ENST00000372007.10	c.431-26A>C		intron_variant	Intron 7 of 17	1	NM_002578.5	ENSP00000361077.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 982442 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 292798

African (AFR) AF: 0.00 AC: 0 AN: 23202

American (AMR) AF: 0.00 AC: 0 AN: 34911

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18544

East Asian (EAS) AF: 0.00 AC: 0 AN: 29553

South Asian (SAS) AF: 0.00 AC: 0 AN: 51345

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40277

Middle Eastern (MID) AF: 0.000258 AC: 1 AN: 3869

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 738510

Other (OTH) AF: 0.00 AC: 0 AN: 42231

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 362

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.33
DANN	Benign	0.39
PhyloP100		-0.77

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

Other links and lift over

dbSNP: rs16986385; hg19: chrX-110395612;