rs775587404

Variant names:

• chr3-48692984-C-A
• rs775587404
• NM_016291.4:c.398G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-48692984-C-A
• chr3-48692984-C-T

Variant summary

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

The NM_016291.4(IP6K2):​c.398G>T​(p.Arg133Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R133H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IP6K2 NM_016291.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.398G>T	p.Arg133Leu	missense	Exon 3 of 6	NP_057375.2	Q9UHH9-1
	IP6K2	NM_001005909.3		c.398G>T	p.Arg133Leu	missense	Exon 3 of 6	NP_001005909.1	Q9UHH9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IP6K2	ENST00000328631.10	TSL:1 MANE Select	c.398G>T	p.Arg133Leu	missense	Exon 3 of 6	ENSP00000331103.5	Q9UHH9-1
	IP6K2	ENST00000479914.5	TSL:1	n.695G>T		non_coding_transcript_exon	Exon 2 of 4
	IP6K2	ENST00000921848.1		c.467G>T	p.Arg156Leu	missense	Exon 4 of 7	ENSP00000591907.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.16
Sift	Benign	0.20	T
Sift4G	Benign	0.39	T
Polyphen		0.068	B
Vest4		0.71
MutPred		0.54		Loss of MoRF binding (P = 0.004)
MVP		0.58
MPC		2.0
ClinPred		0.80	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.60
Mutation Taster		=49/51	disease causing

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: rs775587404; hg19: chr3-48730417;