3-48695257-G-A

Variant names:

• chr3-48695257-G-A
• rs756111244
• NM_016291.4:c.35C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016291.4(IP6K2):​c.35C>T​(p.Pro12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P12H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IP6K2 NM_016291.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

Genes affected

IP6K2 (HGNC:17313): (inositol hexakisphosphate kinase 2) This gene encodes a protein that belongs to the inositol phosphokinase (IPK) family. This protein is likely responsible for the conversion of inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). It may also convert 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4 and affect the growth suppressive and apoptotic activities of interferon-beta in some ovarian cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.107008874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016291.4. 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
	IP6K2	NM_016291.4	MANE Select	c.35C>T	p.Pro12Leu	missense	Exon 2 of 6	NP_057375.2	Q9UHH9-1
	IP6K2	NM_001005909.3		c.35C>T	p.Pro12Leu	missense	Exon 2 of 6	NP_001005909.1	Q9UHH9-1
	IP6K2	NM_001190317.2		c.209C>T	p.Pro70Leu	missense	Exon 3 of 3	NP_001177246.1	Q9UHH9-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IP6K2	ENST00000328631.10	TSL:1 MANE Select	c.35C>T	p.Pro12Leu	missense	Exon 2 of 6	ENSP00000331103.5	Q9UHH9-1
	IP6K2	ENST00000431721.6	TSL:1	c.200C>T	p.Pro67Leu	missense	Exon 3 of 3	ENSP00000414139.2	Q9UHH9-4
	IP6K2	ENST00000340879.8	TSL:1	c.35C>T	p.Pro12Leu	missense	Exon 2 of 3	ENSP00000341925.4	Q9UHH9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434484 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 709466

African (AFR) AF: 0.00 AC: 0 AN: 32778

American (AMR) AF: 0.00 AC: 0 AN: 42178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24840

East Asian (EAS) AF: 0.00 AC: 0 AN: 39212

South Asian (SAS) AF: 0.00 AC: 0 AN: 84190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093888

Other (OTH) AF: 0.00 AC: 0 AN: 58988

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.61	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.057
Sift	Benign	0.10	T
Sift4G	Benign	0.76	T
Polyphen		0.013	B
Vest4		0.14
MutPred		0.34		Loss of catalytic residue at M8 (P = 0.0233)
MVP		0.32
MPC		0.77
ClinPred		0.35	T
GERP RS		3.7
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.070
gMVP		0.18
Mutation Taster		=83/17	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: rs756111244; hg19: chr3-48732690;