22-20781058-T-G

Position:

• chr22-20781058-T-G

Variant summary

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

The NM_058004.4(PI4KA):​c.2328+12135A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,868 control chromosomes in the GnomAD database, including 20,681 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 0.52 (20681 hom., cov: 31)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

Genes affected

PI4KA (HGNC:8983): (phosphatidylinositol 4-kinase alpha) This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2018]

SERPIND1 (HGNC:4838): (serpin family D member 1) This gene belongs to the serpin gene superfamily. Serpins play roles in many processes including inflammation, blood clotting, and cancer metastasis. Members of this family have highly conserved secondary structures with a reactive center loop that interacts with the protease active site to inhibit protease activity. This gene encodes a plasma serine protease that functions as a thrombin and chymotrypsin inhibitor. The protein is activated by heparin, dermatan sulfate, and glycosaminoglycans. Allelic variations in this gene are associated with heparin cofactor II deficiency. [provided by RefSeq, Jul 2015]

PI4KA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI4KA	NM_058004.4	c.2328+12135A>C		intron_variant		ENST00000255882.11	NP_477352.3
SERPIND1	NM_000185.4	c.889+857T>G		intron_variant		ENST00000215727.10	NP_000176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PI4KA	ENST00000255882.11	c.2328+12135A>C		intron_variant		1	NM_058004.4	ENSP00000255882.6
SERPIND1	ENST00000215727.10	c.889+857T>G		intron_variant		1	NM_000185.4	ENSP00000215727.5

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78702 AN: 151752 Hom.: 20663 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.519 AC: 78775 AN: 151868 Hom.: 20681 Cov.: 31 AF XY: 0.513 AC XY: 38097 AN XY: 74194

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.525

Alfa AF: 0.490 Hom.: 24315

Bravo AF: 0.533

Asia WGS AF: 0.447 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.7
DANN	Benign	0.74

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: rs165862; hg19: chr22-21135346;