10-104315026-C-A

Variant names:

• chr10-104315026-C-A
• rs765763980
• NM_001272013.2:c.1026G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001272013.2(ITPRIP):​c.1026G>T​(p.Lys342Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: ITPRIP NM_001272013.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.590
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1026G>T	p.Lys342Asn	missense	Exon 2 of 2	NP_001258942.1	Q8IWB1
	ITPRIP	NM_001272012.2		c.1026G>T	p.Lys342Asn	missense	Exon 2 of 2	NP_001258941.1	Q8IWB1
	ITPRIP	NM_033397.4		c.1026G>T	p.Lys342Asn	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.1026G>T	p.Lys342Asn	missense	Exon 2 of 2	ENSP00000337178.1	Q8IWB1
	ITPRIP	ENST00000278071.6	TSL:1	c.1026G>T	p.Lys342Asn	missense	Exon 3 of 3	ENSP00000278071.2	Q8IWB1
	ITPRIP	ENST00000358187.2	TSL:2	c.1026G>T	p.Lys342Asn	missense	Exon 2 of 2	ENSP00000350915.2	Q8IWB1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251348 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000821 AC: 12 AN: 1461848 Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8 AN XY: 727228

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

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	0.74
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.59
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.45		Loss of methylation at K342 (P = 0.0027)
MVP		0.19
MPC		0.87
ClinPred		0.88	D
GERP RS		4.1
Varity_R		0.39
gMVP		0.57
Mutation Taster		=53/47	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: rs765763980; hg19: chr10-106074784; COSMIC: COSV105117951; COSMIC: COSV105117951;