4-25234173-C-T

Variant names:

• chr4-25234173-C-T
• rs863223383
• NM_018323.4:c.10C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018323.4(PI4K2B):​c.10C>T​(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,225,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000016 (0 hom.)
• Consequence: PI4K2B NM_018323.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050697744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2B	NM_018323.4	c.10C>T	p.Pro4Ser	missense_variant	Exon 1 of 10	ENST00000264864.8	NP_060793.2
PI4K2B	XM_005248174.3	c.10C>T	p.Pro4Ser	missense_variant	Exon 1 of 10		XP_005248231.1
PI4K2B	NR_144633.2	n.141C>T		non_coding_transcript_exon_variant	Exon 1 of 10
PI4K2B	XR_007057941.1	n.141C>T		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.10C>T	p.Pro4Ser	missense_variant	Exon 1 of 10	1	NM_018323.4	ENSP00000264864.6
PI4K2B	ENST00000512921.4	c.-20-18148C>T		intron_variant	Intron 1 of 9	2		ENSP00000423373.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000163 AC: 2 AN: 1225760 Hom.: 0 Cov.: 30 AF XY: 0.00000336 AC XY: 2 AN XY: 594868

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: 0.00000201

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.058
Sift	Benign	0.11	T
Sift4G	Benign	0.80	T
Polyphen		0.0030	B
Vest4		0.056
MutPred		0.31		Gain of glycosylation at S5 (P = 0.0017);
MVP		0.20
MPC		0.32
ClinPred		0.15	T
GERP RS		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.034
gMVP		0.092

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

LitVar

Other links and lift over

dbSNP: rs863223383; hg19: chr4-25235795;