19-39150506-A-G

Variant names:

• chr19-39150506-A-G
• rs513053
• NM_005884.5:c.-95-17724A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005884.5(PAK4):​c.-95-17724A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,818 control chromosomes in the GnomAD database, including 28,970 homozygotes. 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: 𝑓 0.62 (28970 hom., cov: 30)
• Consequence: PAK4 NM_005884.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 6 publications found

Genes affected

PAK4 (HGNC:16059): (p21 (RAC1) activated kinase 4) PAK proteins, a family of serine/threonine p21-activating kinases, include PAK1, PAK2, PAK3 and PAK4. PAK proteins are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. They serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK4 interacts specifically with the GTP-bound form of Cdc42Hs and weakly activates the JNK family of MAP kinases. PAK4 is a mediator of filopodia formation and may play a role in the reorganization of the actin cytoskeleton. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005884.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK4	NM_005884.5	MANE Select	c.-95-17724A>G		intron	N/A	NP_005875.1
	PAK4	NM_001014831.3		c.-321-17724A>G		intron	N/A	NP_001014831.1
	PAK4	NM_001014832.2		c.-22-19026A>G		intron	N/A	NP_001014832.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAK4	ENST00000360442.8	TSL:5 MANE Select	c.-95-17724A>G		intron	N/A	ENSP00000353625.3
	PAK4	ENST00000358301.7	TSL:1	c.-22-19026A>G		intron	N/A	ENSP00000351049.2
	PAK4	ENST00000593690.5	TSL:1	c.-321-17724A>G		intron	N/A	ENSP00000469413.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93329 AN: 151700 Hom.: 28956 Cov.: 30

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.653

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.615 AC: 93389 AN: 151818 Hom.: 28970 Cov.: 30 AF XY: 0.613 AC XY: 45507 AN XY: 74186

African (AFR) AF: 0.579 AC: 23958 AN: 41366

American (AMR) AF: 0.554 AC: 8448 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2604 AN: 3470

East Asian (EAS) AF: 0.823 AC: 4243 AN: 5156

South Asian (SAS) AF: 0.644 AC: 3094 AN: 4802

European-Finnish (FIN) AF: 0.588 AC: 6187 AN: 10520

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42726 AN: 67950

Other (OTH) AF: 0.651 AC: 1370 AN: 2104

Alfa AF: 0.617 Hom.: 11733

Bravo AF: 0.611

Asia WGS AF: 0.686 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.51
DANN	Benign	0.31
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs513053; hg19: chr19-39641146; COSMIC: COSV58945268;