6-33722893-C-G

Variant names:

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

Variant summary

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

The NM_054111.5(IP6K3):​c.1060G>C​(p.Gly354Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 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. 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. G354S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IP6K3 NM_054111.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 0 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: 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=0.15145856).

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>C	p.Gly354Arg	missense	Exon 6 of 6	NP_473452.2	Q5TAQ4
	IP6K3	NM_001142883.2		c.1060G>C	p.Gly354Arg	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>C	p.Gly354Arg	missense	Exon 6 of 6	ENSP00000293756.4	Q96PC2
	IP6K3	ENST00000451316.6	TSL:2	c.1060G>C	p.Gly354Arg	missense	Exon 7 of 7	ENSP00000398861.1	Q96PC2
	IP6K3	ENST00000885829.1		c.1060G>C	p.Gly354Arg	missense	Exon 6 of 6	ENSP00000555888.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

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

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.7
DANN	Benign	0.89
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.44
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.065
Sift	Benign	0.39	T
Sift4G	Benign	0.50	T
Polyphen		0.95	P
Vest4		0.16
MutPred		0.43		Gain of solvent accessibility (P = 0.0037)
MVP		0.38
MPC		0.25
ClinPred		0.31	T
GERP RS		-1.2
Varity_R		0.041
gMVP		0.20
Mutation Taster		=95/5	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;