3-49727498-C-A

Variant names:

• chr3-49727498-C-A
• NM_153273.4:c.950G>T

Variant summary

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

The NM_153273.4(IP6K1):​c.950G>T​(p.Gly317Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IP6K1 NM_153273.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64
• 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=0.2957961).

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.950G>T	p.Gly317Val	missense	Exon 6 of 6	NP_695005.1	Q92551-1
	IP6K1	NM_001242829.2		c.950G>T	p.Gly317Val	missense	Exon 6 of 6	NP_001229758.1	Q92551-1
	IP6K1	NM_001006115.3		c.455G>T	p.Gly152Val	missense	Exon 5 of 5	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.950G>T	p.Gly317Val	missense	Exon 6 of 6	ENSP00000323780.4	Q92551-1
	IP6K1	ENST00000613416.4	TSL:5	c.950G>T	p.Gly317Val	missense	Exon 6 of 6	ENSP00000482032.1	Q92551-1
	IP6K1	ENST00000853567.1		c.950G>T	p.Gly317Val	missense	Exon 7 of 7	ENSP00000523626.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Benign	0.068
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.12
Sift	Benign	0.22	T
Sift4G	Benign	0.21	T
Polyphen		0.095	B
Vest4		0.26
MutPred		0.30		Gain of glycosylation at S313 (P = 0.0674)
MVP		0.37
MPC		1.2
ClinPred		0.44	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.32
Mutation Taster		=62/38	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

hg19: chr3-49764931;