10-104314890-C-T

Variant names:

• chr10-104314890-C-T
• NM_001272013.2:c.1162G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001272013.2(ITPRIP):​c.1162G>A​(p.Glu388Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITPRIP NM_001272013.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84

Genes affected

ITPRIP (HGNC:29370): (inositol 1,4,5-trisphosphate receptor interacting protein) This gene encodes a membrane-associated protein that binds the inositol 1,4,5-trisphosphate receptor (ITPR). The encoded protein enhances the sensitivity of ITPR to intracellular calcium signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRIP	NM_001272013.2	c.1162G>A	p.Glu388Lys	missense_variant	Exon 2 of 2	ENST00000337478.3	NP_001258942.1
ITPRIP	NM_001272012.2	c.1162G>A	p.Glu388Lys	missense_variant	Exon 2 of 2		NP_001258941.1
ITPRIP	NM_033397.4	c.1162G>A	p.Glu388Lys	missense_variant	Exon 3 of 3		NP_203755.1
ITPRIP	XM_005270257.3	c.1177G>A	p.Glu393Lys	missense_variant	Exon 2 of 2		XP_005270314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPRIP	ENST00000337478.3	c.1162G>A	p.Glu388Lys	missense_variant	Exon 2 of 2	1	NM_001272013.2	ENSP00000337178.1
ITPRIP	ENST00000278071.6	c.1162G>A	p.Glu388Lys	missense_variant	Exon 3 of 3	1		ENSP00000278071.2
ITPRIP	ENST00000358187.2	c.1162G>A	p.Glu388Lys	missense_variant	Exon 2 of 2	2		ENSP00000350915.2
ITPRIP	ENST00000647721.1	c.1162G>A	p.Glu388Lys	missense_variant	Exon 3 of 3			ENSP00000497746.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461392 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727018

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1162G>A (p.E388K) alteration is located in exon 3 (coding exon 1) of the ITPRIP gene. This alteration results from a G to A substitution at nucleotide position 1162, causing the glutamic acid (E) at amino acid position 388 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.46	T;T;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;.;.;.
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.96	D;D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	3.4	M;M;M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-4.0	D;D;D;.
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		1.0	D;D;D;D
Vest4		0.95
MutPred		0.81		Gain of methylation at E388 (P = 0.0124);Gain of methylation at E388 (P = 0.0124);Gain of methylation at E388 (P = 0.0124);Gain of methylation at E388 (P = 0.0124);
MVP		0.12
MPC		0.85
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.85
gMVP		0.92

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-106074648;