X-111123183-C-T

Variant names:

• chrX-111123183-C-T
• NM_002578.5:c.80C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002578.5(PAK3):​c.80C>T​(p.Ala27Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000921 in 1,086,332 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: 24)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: PAK3 NM_002578.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.28

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38700724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAK3	NM_002578.5	c.80C>T	p.Ala27Val	missense_variant	Exon 5 of 18	ENST00000372007.10	NP_002569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAK3	ENST00000372007.10	c.80C>T	p.Ala27Val	missense_variant	Exon 5 of 18	1	NM_002578.5	ENSP00000361077.4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.21e-7 AC: 1 AN: 1086332 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 352108

Gnomad4 AFR exome AF: 0.0000382

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	.;.;T;.;.;.;T;.;.;T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	.;D;.;.;.;.;D;D;D;D
M_CAP	Pathogenic	0.59	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.66	N;N;N;N;N;N;.;N;N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.52	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.38	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.39	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;B;.;B;B;B
Vest4		0.32
MutPred		0.043		Gain of MoRF binding (P = 0.1529);Gain of MoRF binding (P = 0.1529);Gain of MoRF binding (P = 0.1529);Gain of MoRF binding (P = 0.1529);Gain of MoRF binding (P = 0.1529);Gain of MoRF binding (P = 0.1529);Gain of MoRF binding (P = 0.1529);Gain of MoRF binding (P = 0.1529);Gain of MoRF binding (P = 0.1529);Gain of MoRF binding (P = 0.1529);
MVP		0.67
MPC		1.1
ClinPred		0.73	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-110366411;