NM_001272013.2:c.1105C>T

Variant names:

• chr10-104314947-G-A
• rs754329412
• NM_001272013.2:c.1105C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001272013.2(ITPRIP):​c.1105C>T​(p.Pro369Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P369T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITPRIP NM_001272013.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054934293).

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.1105C>T	p.Pro369Ser	missense	Exon 2 of 2	NP_001258942.1	Q8IWB1
	ITPRIP	NM_001272012.2		c.1105C>T	p.Pro369Ser	missense	Exon 2 of 2	NP_001258941.1	Q8IWB1
	ITPRIP	NM_033397.4		c.1105C>T	p.Pro369Ser	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.1105C>T	p.Pro369Ser	missense	Exon 2 of 2	ENSP00000337178.1	Q8IWB1
	ITPRIP	ENST00000278071.6	TSL:1	c.1105C>T	p.Pro369Ser	missense	Exon 3 of 3	ENSP00000278071.2	Q8IWB1
	ITPRIP	ENST00000358187.2	TSL:2	c.1105C>T	p.Pro369Ser	missense	Exon 2 of 2	ENSP00000350915.2	Q8IWB1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248970 AF XY: 0.00000740

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461342 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726990

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

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.32
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.14
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.077
Sift	Benign	0.44	T
Sift4G	Benign	1.0	T
Polyphen		0.27	B
Vest4		0.025
MutPred		0.23		Gain of phosphorylation at P369 (P = 0.0198)
MVP		0.076
MPC		0.21
ClinPred		0.11	T
GERP RS		3.8
Varity_R		0.029
gMVP		0.12
Mutation Taster		=96/4	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

dbSNP: rs754329412; hg19: chr10-106074705; COSMIC: COSV53391542; COSMIC: COSV53391542;