chr6-33738702-C-T

Variant names:

• chr6-33738702-C-T
• rs9469578
• NM_054111.5:c.-179-3047G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054111.5(IP6K3):​c.-179-3047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,148 control chromosomes in the GnomAD database, including 1,155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1155 hom., cov: 32)
• Consequence: IP6K3 NM_054111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 22 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IP6K3	NM_054111.5	MANE Select	c.-179-3047G>A		intron	N/A	NP_473452.2
	IP6K3	NM_001142883.2		c.-180+431G>A		intron	N/A	NP_001136355.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IP6K3	ENST00000293756.5	TSL:1 MANE Select	c.-179-3047G>A		intron	N/A	ENSP00000293756.4
	IP6K3	ENST00000451316.6	TSL:2	c.-180+431G>A		intron	N/A	ENSP00000398861.1
	IP6K3	ENST00000634274.1	TSL:4	c.-179-3047G>A		intron	N/A	ENSP00000489479.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16404 AN: 152030 Hom.: 1152 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0883

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0445

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.108 AC: 16438 AN: 152148 Hom.: 1155 Cov.: 32 AF XY: 0.108 AC XY: 8058 AN XY: 74382

African (AFR) AF: 0.193 AC: 8009 AN: 41484

American (AMR) AF: 0.0881 AC: 1347 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3472

East Asian (EAS) AF: 0.0446 AC: 231 AN: 5176

South Asian (SAS) AF: 0.0736 AC: 355 AN: 4822

European-Finnish (FIN) AF: 0.0948 AC: 1004 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0713 AC: 4850 AN: 67998

Other (OTH) AF: 0.107 AC: 225 AN: 2106

Alfa AF: 0.0835 Hom.: 1681

Bravo AF: 0.111

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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: rs9469578; hg19: chr6-33706479;