chr3-49747848-C-T

Variant names:

• chr3-49747848-C-T
• rs751128846
• NM_153273.4:c.193G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153273.4(IP6K1):​c.193G>A​(p.Glu65Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: IP6K1 NM_153273.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

IP6K1 (HGNC:18360): (inositol hexakisphosphate kinase 1) This gene encodes a member of the inositol phosphokinase family. The encoded protein may be 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. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41988522).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153273.4. 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
	IP6K1	NM_153273.4	MANE Select	c.193G>A	p.Glu65Lys	missense	Exon 2 of 6	NP_695005.1	Q92551-1
	IP6K1	NM_001242829.2		c.193G>A	p.Glu65Lys	missense	Exon 2 of 6	NP_001229758.1	Q92551-1
	IP6K1	NM_001006115.3		c.-272-9426G>A		intron	N/A	NP_001006115.1	Q92551-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IP6K1	ENST00000321599.9	TSL:1 MANE Select	c.193G>A	p.Glu65Lys	missense	Exon 2 of 6	ENSP00000323780.4	Q92551-1
	IP6K1	ENST00000613416.4	TSL:5	c.193G>A	p.Glu65Lys	missense	Exon 2 of 6	ENSP00000482032.1	Q92551-1
	IP6K1	ENST00000853567.1		c.193G>A	p.Glu65Lys	missense	Exon 3 of 7	ENSP00000523626.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251408 AF XY: 0.0000147

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727230

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

American (AMR) AF: 0.0000224 AC: 1 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: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74298

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.19
Sift	Benign	0.12	T
Sift4G	Benign	0.22	T
Polyphen		0.67	P
Vest4		0.60
MutPred		0.37		Loss of glycosylation at P64 (P = 0.0156)
MVP		0.75
MPC		1.5
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.29
gMVP		0.84
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs751128846; hg19: chr3-49785281;