22-20710099-C-T

Variant names:

• chr22-20710099-C-T
• rs5760150
• NM_058004.4:c.6084-102G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058004.4(PI4KA):​c.6084-102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 693,592 control chromosomes in the GnomAD database, including 9,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1827 hom., cov: 33)
  • Exomes 𝑓: 0.16 (7358 hom.)
• Consequence: PI4KA NM_058004.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.368
• Publications: 1 publications found

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]

PI4KA Gene-Disease associations (from GenCC):

• polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-20710099-C-T is Benign according to our data. Variant chr22-20710099-C-T is described in ClinVar as Benign. ClinVar VariationId is 1297977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058004.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4KA	NM_058004.4	MANE Select	c.6084-102G>A		intron	N/A	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.6018-102G>A		intron	N/A	NP_001349792.1
	PI4KA	NM_001362862.2		c.5991-102G>A		intron	N/A	NP_001349791.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4KA	ENST00000255882.11	TSL:1 MANE Select	c.6084-102G>A		intron	N/A	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000477245.5	TSL:1	n.2457-102G>A		intron	N/A
	PI4KA	ENST00000939414.1		c.6120-102G>A		intron	N/A	ENSP00000609473.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22772 AN: 151990 Hom.: 1828 Cov.: 33

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.157 AC: 85197 AN: 541484 Hom.: 7358 Cov.: 5 AF XY: 0.154 AC XY: 45033 AN XY: 291816

African (AFR) AF: 0.103 AC: 1514 AN: 14742

American (AMR) AF: 0.132 AC: 3844 AN: 29130

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 4860 AN: 17396

East Asian (EAS) AF: 0.0703 AC: 2247 AN: 31948

South Asian (SAS) AF: 0.0729 AC: 4364 AN: 59834

European-Finnish (FIN) AF: 0.124 AC: 5814 AN: 46912

Middle Eastern (MID) AF: 0.215 AC: 662 AN: 3078

European-Non Finnish (NFE) AF: 0.184 AC: 56866 AN: 309102

Other (OTH) AF: 0.171 AC: 5026 AN: 29342

GnomAD4 genome AF: 0.150 AC: 22770 AN: 152108 Hom.: 1827 Cov.: 33 AF XY: 0.148 AC XY: 11015 AN XY: 74348

African (AFR) AF: 0.0983 AC: 4085 AN: 41544

American (AMR) AF: 0.163 AC: 2489 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 963 AN: 3458

East Asian (EAS) AF: 0.0749 AC: 387 AN: 5164

South Asian (SAS) AF: 0.0708 AC: 341 AN: 4814

European-Finnish (FIN) AF: 0.117 AC: 1245 AN: 10604

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12538 AN: 67930

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.174 Hom.: 269

Bravo AF: 0.153

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.77
PhyloP100		0.37
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: rs5760150; hg19: chr22-21064387; COSMIC: COSV55406982; COSMIC: COSV55406982;