rs13471

Variant names:

• chr22-20707980-G-T
• rs13471
• NM_058004.4:c.*67C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-20707980-G-T
• chr22-20707980-G-A
• chr22-20707980-G-C

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.*67C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,356,082 control chromosomes in the GnomAD database, including 3,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (306 hom., cov: 30)
  • Exomes 𝑓: 0.072 (3250 hom.)
• Consequence: PI4KA NM_058004.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.62
• Publications: 8 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=-0.9).
• BP6: Variant 22-20707980-G-T is Benign according to our data. Variant chr22-20707980-G-T is described in ClinVar as Benign. ClinVar VariationId is 1262196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.074 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.*67C>A		3_prime_UTR	Exon 55 of 55	NP_477352.3	P42356-1
	PI4KA	NM_001362863.2		c.*67C>A		3_prime_UTR	Exon 54 of 54	NP_001349792.1
	PI4KA	NM_001362862.2		c.*67C>A		3_prime_UTR	Exon 54 of 54	NP_001349791.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4KA	ENST00000255882.11	TSL:1 MANE Select	c.*67C>A		3_prime_UTR	Exon 55 of 55	ENSP00000255882.6	P42356-1
	PI4KA	ENST00000477245.5	TSL:1	n.2749C>A		non_coding_transcript_exon	Exon 23 of 23
	PI4KA	ENST00000939414.1		c.*67C>A		3_prime_UTR	Exon 56 of 56	ENSP00000609473.1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9577 AN: 152130 Hom.: 307 Cov.: 30

Gnomad AFR AF: 0.0451

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.0643

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.0621

GnomAD4 exome AF: 0.0720 AC: 86618 AN: 1203834 Hom.: 3250 Cov.: 17 AF XY: 0.0714 AC XY: 43675 AN XY: 611724

African (AFR) AF: 0.0476 AC: 1348 AN: 28290

American (AMR) AF: 0.0725 AC: 3217 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.0293 AC: 722 AN: 24622

East Asian (EAS) AF: 0.0662 AC: 2550 AN: 38540

South Asian (SAS) AF: 0.0664 AC: 5393 AN: 81214

European-Finnish (FIN) AF: 0.0553 AC: 2947 AN: 53266

Middle Eastern (MID) AF: 0.0503 AC: 213 AN: 4232

European-Non Finnish (NFE) AF: 0.0761 AC: 66737 AN: 877532

Other (OTH) AF: 0.0674 AC: 3491 AN: 51792

GnomAD4 genome AF: 0.0629 AC: 9581 AN: 152248 Hom.: 306 Cov.: 30 AF XY: 0.0624 AC XY: 4646 AN XY: 74446

African (AFR) AF: 0.0451 AC: 1875 AN: 41558

American (AMR) AF: 0.0598 AC: 915 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3472

East Asian (EAS) AF: 0.0785 AC: 405 AN: 5162

South Asian (SAS) AF: 0.0654 AC: 316 AN: 4830

European-Finnish (FIN) AF: 0.0585 AC: 621 AN: 10612

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5150 AN: 67984

Other (OTH) AF: 0.0619 AC: 131 AN: 2116

Alfa AF: 0.0566 Hom.: 129

Bravo AF: 0.0612

Asia WGS AF: 0.0600 AC: 208 AN: 3478

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	-0.90
CADD	Benign	0.039
DANN	Benign	0.53
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs13471; hg19: chr22-21062268; COSMIC: COSV55403608; COSMIC: COSV55403608;