6-33722893-C-T

Variant names:

• chr6-33722893-C-T
• rs369669636
• NM_054111.5:c.1060G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_054111.5(IP6K3):​c.1060G>A​(p.Gly354Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,613,950 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 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: IP6K3 NM_054111.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.439
• Publications: 1 publications found

Genes affected

IP6K3 (HGNC:17269): (inositol hexakisphosphate kinase 3) 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. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Dec 2008]

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=0.05618137).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054111.5. 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
	IP6K3	NM_054111.5	MANE Select	c.1060G>A	p.Gly354Ser	missense	Exon 6 of 6	NP_473452.2	Q5TAQ4
	IP6K3	NM_001142883.2		c.1060G>A	p.Gly354Ser	missense	Exon 7 of 7	NP_001136355.1	Q96PC2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IP6K3	ENST00000293756.5	TSL:1 MANE Select	c.1060G>A	p.Gly354Ser	missense	Exon 6 of 6	ENSP00000293756.4	Q96PC2
	IP6K3	ENST00000451316.6	TSL:2	c.1060G>A	p.Gly354Ser	missense	Exon 7 of 7	ENSP00000398861.1	Q96PC2
	IP6K3	ENST00000885829.1		c.1060G>A	p.Gly354Ser	missense	Exon 6 of 6	ENSP00000555888.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152058 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251470 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000791

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000554 AC: 81 AN: 1461892 Hom.: 0 Cov.: 30 AF XY: 0.0000468 AC XY: 34 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000683 AC: 76 AN: 1112012

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152058 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74268

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.000296

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	0.070
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.24
DANN	Benign	0.51
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.44
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.0020
Sift	Benign	0.79	T
Sift4G	Benign	0.78	T
Polyphen		0.14	B
Vest4		0.096
MVP		0.17
MPC		0.20
ClinPred		0.017	T
GERP RS		-1.2
Varity_R		0.031
gMVP		0.15
Mutation Taster		=96/4	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: rs369669636; hg19: chr6-33690670; COSMIC: COSV53389145;