22-21483071-C-T

Variant names:

• chr22-21483071-C-T
• rs2930770
• ENST00000462560.6:n.697G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000462560.6(ENSG00000293427):​n.697G>A variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. 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 0.000030 (0 hom., cov: 16)
  • Exomes 𝑓: 0.000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000293427 ENST00000462560.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.35
• Publications: 2 publications found

Genes affected

ENSG00000293427 (HGNC:):

PI4KAP2 (HGNC:33577): (phosphatidylinositol 4-kinase alpha pseudogene 2) Predicted to enable 1-phosphatidylinositol 4-kinase activity. Predicted to be involved in phosphatidylinositol phosphate biosynthetic process and phosphatidylinositol-mediated signaling. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462560.6. 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
	PI4KAP2	NR_003700.1		n.964G>A		non_coding_transcript_exon	Exon 8 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000293427	ENST00000462560.6	TSL:1	n.697G>A		non_coding_transcript_exon	Exon 6 of 15
	ENSG00000293427	ENST00000479693.1	TSL:1	n.993G>A		non_coding_transcript_exon	Exon 8 of 13
	PI4KAP2	ENST00000360806.9	TSL:6	n.673G>A		non_coding_transcript_exon	Exon 6 of 16

Frequencies

GnomAD3 genomes AF: 0.0000297 AC: 4 AN: 134606 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000489

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000188 AC: 3 AN: 159696 AF XY: 0.0000237

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000324

Gnomad OTH exome AF: 0.000224

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000174 AC: 23 AN: 1321968 Hom.: 0 Cov.: 24 AF XY: 0.0000168 AC XY: 11 AN XY: 654310

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31576

American (AMR) AF: 0.00 AC: 0 AN: 34590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24464

East Asian (EAS) AF: 0.00 AC: 0 AN: 32492

South Asian (SAS) AF: 0.0000256 AC: 2 AN: 78238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47386

Middle Eastern (MID) AF: 0.000197 AC: 1 AN: 5082

European-Non Finnish (NFE) AF: 0.0000148 AC: 15 AN: 1013500

Other (OTH) AF: 0.0000915 AC: 5 AN: 54640

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000888178), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000297 AC: 4 AN: 134606 Hom.: 0 Cov.: 16 AF XY: 0.0000154 AC XY: 1 AN XY: 64748

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000257 AC: 1 AN: 38924

American (AMR) AF: 0.00 AC: 0 AN: 11724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3248

East Asian (EAS) AF: 0.00 AC: 0 AN: 3866

South Asian (SAS) AF: 0.00 AC: 0 AN: 3714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000489 AC: 3 AN: 61290

Other (OTH) AF: 0.00 AC: 0 AN: 1786

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0332287), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000480 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.90
PhyloP100		7.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2930770; hg19: chr22-21837360;