3-48695257-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_016291.4(IP6K2):​c.35C>A​(p.Pro12His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000693 in 1,586,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: IP6K2 NM_016291.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044527143).
• BS2: High AC in GnomAd4 at 7 AD gene.

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>A	p.Pro12His	missense	Exon 2 of 6	NP_057375.2	Q9UHH9-1
	IP6K2	NM_001005909.3		c.35C>A	p.Pro12His	missense	Exon 2 of 6	NP_001005909.1	Q9UHH9-1
	IP6K2	NM_001190317.2		c.209C>A	p.Pro70His	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>A	p.Pro12His	missense	Exon 2 of 6	ENSP00000331103.5	Q9UHH9-1
	IP6K2	ENST00000431721.6	TSL:1	c.200C>A	p.Pro67His	missense	Exon 3 of 3	ENSP00000414139.2	Q9UHH9-4
	IP6K2	ENST00000340879.8	TSL:1	c.35C>A	p.Pro12His	missense	Exon 2 of 3	ENSP00000341925.4	Q9UHH9-2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000839 AC: 2 AN: 238280 AF XY: 0.00000777

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000620

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1434484 Hom.: 0 Cov.: 33 AF XY: 0.00000423 AC XY: 3 AN XY: 709466

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

American (AMR) AF: 0.0000237 AC: 1 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: 0.00 AC: 0 AN: 1093888

Other (OTH) AF: 0.0000509 AC: 3 AN: 58988

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.000458 AC: 7 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.36	N
PhyloP100		2.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.044
Sift	Benign	0.42	T
Sift4G	Benign	0.63	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.24		Gain of helix (P = 0.0199)
MVP		0.29
MPC		0.86
ClinPred		0.12	T
GERP RS		3.7
PromoterAI		-0.0014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.17
Mutation Taster		=75/25	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;