11-77467875-A-T

Position:

• chr11-77467875-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002576.5(PAK1):​c.-22+5677T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,110 control chromosomes in the GnomAD database, including 38,169 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 0.70 (38169 hom., cov: 33)
• Consequence: PAK1 NM_002576.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

Genes affected

PAK1 (HGNC:8590): (p21 (RAC1) activated kinase 1) This gene encodes a family member of serine/threonine p21-activating kinases, known as PAK proteins. These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. This specific family member regulates cell motility and morphology. Mutations in this gene have been associated with macrocephaly, seizures, and speech delay. Overexpression of this gene is also reported in many cancer types, and particularly in breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2020]

PAK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAK1	NM_002576.5	c.-22+5677T>A		intron_variant		ENST00000356341.8	NP_002567.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAK1	ENST00000356341.8	c.-22+5677T>A		intron_variant		1	NM_002576.5	ENSP00000348696.4

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106439 AN: 151994 Hom.: 38134 Cov.: 33

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.700 AC: 106523 AN: 152110 Hom.: 38169 Cov.: 33 AF XY: 0.696 AC XY: 51742 AN XY: 74368

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.686

Alfa AF: 0.671 Hom.: 4100

Bravo AF: 0.695

Asia WGS AF: 0.603 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs3015993; hg19: chr11-77178920;