NM_018323.4:c.124G>A

Variant names:

• chr4-25234287-G-A
• NM_018323.4:c.124G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018323.4(PI4K2B):​c.124G>A​(p.Ala42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000079 in 1,266,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: PI4K2B NM_018323.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38

Genes affected

PI4K2B (HGNC:18215): (phosphatidylinositol 4-kinase type 2 beta) This gene encodes a member of the type II PI4 kinase protein family. The encoded protein is primarily cytosolic and contributes to overall PI4-kinase activity along with other protein family members. This protein is involved in early T cell activation. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21669477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2B	NM_018323.4	c.124G>A	p.Ala42Thr	missense_variant	Exon 1 of 10	ENST00000264864.8	NP_060793.2
PI4K2B	XM_005248174.3	c.124G>A	p.Ala42Thr	missense_variant	Exon 1 of 10		XP_005248231.1
PI4K2B	NR_144633.2	n.255G>A		non_coding_transcript_exon_variant	Exon 1 of 10
PI4K2B	XR_007057941.1	n.255G>A		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2B	ENST00000264864.8	c.124G>A	p.Ala42Thr	missense_variant	Exon 1 of 10	1	NM_018323.4	ENSP00000264864.6
PI4K2B	ENST00000512921.4	c.-20-18034G>A		intron_variant	Intron 1 of 9	2		ENSP00000423373.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.90e-7 AC: 1 AN: 1266442 Hom.: 0 Cov.: 31 AF XY: 0.00000162 AC XY: 1 AN XY: 618802

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.86e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.075
Sift	Benign	0.14	T
Sift4G	Benign	0.50	T
Polyphen		0.97	D
Vest4		0.092
MutPred		0.21		Gain of glycosylation at S45 (P = 0.0763);
MVP		0.55
MPC		1.0
ClinPred		0.48	T
GERP RS		2.4
Varity_R		0.079
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-25235909;