chr4-25234173-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4T) has been classified as Benign.

• 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
• Publications: 0 publications found

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

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018323.4. 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
	PI4K2B	NM_018323.4	MANE Select	c.10C>T	p.Pro4Ser	missense	Exon 1 of 10	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.141C>T		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2B	ENST00000264864.8	TSL:1 MANE Select	c.10C>T	p.Pro4Ser	missense	Exon 1 of 10	ENSP00000264864.6	Q8TCG2
	PI4K2B	ENST00000871538.1		c.10C>T	p.Pro4Ser	missense	Exon 1 of 11	ENSP00000541597.1
	PI4K2B	ENST00000963199.1		c.10C>T	p.Pro4Ser	missense	Exon 1 of 10	ENSP00000633258.1

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

African (AFR) AF: 0.00 AC: 0 AN: 24968

American (AMR) AF: 0.00 AC: 0 AN: 15352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17414

East Asian (EAS) AF: 0.00 AC: 0 AN: 28058

South Asian (SAS) AF: 0.00 AC: 0 AN: 54536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4538

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 996570

Other (OTH) AF: 0.00 AC: 0 AN: 49950

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.62
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
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.034
gMVP		0.092
Mutation Taster		=94/6	polymorphism

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: rs863223383; hg19: chr4-25235795;