NM_001272013.2:c.1319T>C

Variant names:

• chr10-104314733-A-G
• rs761327165
• NM_001272013.2:c.1319T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001272013.2(ITPRIP):​c.1319T>C​(p.Leu440Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,506 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: 0.0000048 (0 hom.)
• Consequence: ITPRIP NM_001272013.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.24
• Publications: 0 publications found

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]

ITPRIP-AS1 (HGNC:54100): (ITPRIP antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.867

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001272013.2. 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
	ITPRIP	NM_001272013.2	MANE Select	c.1319T>C	p.Leu440Pro	missense	Exon 2 of 2	NP_001258942.1	Q8IWB1
	ITPRIP	NM_001272012.2		c.1319T>C	p.Leu440Pro	missense	Exon 2 of 2	NP_001258941.1	Q8IWB1
	ITPRIP	NM_033397.4		c.1319T>C	p.Leu440Pro	missense	Exon 3 of 3	NP_203755.1	Q8IWB1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIP	ENST00000337478.3	TSL:1 MANE Select	c.1319T>C	p.Leu440Pro	missense	Exon 2 of 2	ENSP00000337178.1	Q8IWB1
	ITPRIP	ENST00000278071.6	TSL:1	c.1319T>C	p.Leu440Pro	missense	Exon 3 of 3	ENSP00000278071.2	Q8IWB1
	ITPRIP	ENST00000358187.2	TSL:2	c.1319T>C	p.Leu440Pro	missense	Exon 2 of 2	ENSP00000350915.2	Q8IWB1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250084 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461506 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727038

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

American (AMR) AF: 0.000157 AC: 7 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111882

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 33

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	0.90
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		9.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.67		Loss of stability (P = 0.0148)
MVP		0.49
MPC		1.0
ClinPred		0.97	D
GERP RS		4.9
Varity_R		0.95
gMVP		0.85
Mutation Taster		=26/74	disease causing

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: rs761327165; hg19: chr10-106074491;