chr10-97656843-T-C

Variant names:

• chr10-97656843-T-C
• rs1034098630
• NM_018425.4:c.791T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_Strong BS2

The NM_018425.4(PI4K2A):​c.791T>C​(p.Val264Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PI4K2A NM_018425.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

Genes affected

PI4K2A (HGNC:30031): (phosphatidylinositol 4-kinase type 2 alpha) Phosphatidylinositolpolyphosphates (PtdInsPs) are centrally involved in many biologic processes, ranging from cell growth and organization of the actin cytoskeleton to endo- and exocytosis. PI4KII phosphorylates PtdIns at the D-4 position, an essential step in the biosynthesis of PtdInsPs (Barylko et al., 2001 [PubMed 11244087]).[supplied by OMIM, Mar 2008]

ENSG00000249967 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2A	NM_018425.4	c.791T>C	p.Val264Ala	missense_variant	Exon 4 of 9	ENST00000370631.4	NP_060895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2A	ENST00000370631.4	c.791T>C	p.Val264Ala	missense_variant	Exon 4 of 9	1	NM_018425.4	ENSP00000359665.3
ENSG00000249967	ENST00000370649.3	c.701T>C	p.Val234Ala	missense_variant	Exon 5 of 10	2		ENSP00000359683.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.791T>C (p.V264A) alteration is located in exon 4 (coding exon 4) of the PI4K2A gene. This alteration results from a T to C substitution at nucleotide position 791, causing the valine (V) at amino acid position 264 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	.;D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Pathogenic	3.6	.;H
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.8	D;D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.90	.;P
Vest4		0.86
MutPred		0.82		.;Loss of ubiquitination at K268 (P = 0.1576);
MVP		0.66
MPC		2.3
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.72
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1034098630; hg19: chr10-99416600;