chr10-104314871-G-A

Variant names:

• chr10-104314871-G-A
• rs368032423
• NM_001272013.2:c.1181C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001272013.2(ITPRIP):​c.1181C>T​(p.Thr394Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,613,722 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: ITPRIP NM_001272013.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.452
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044696927).
• BP6: Variant 10-104314871-G-A is Benign according to our data. Variant chr10-104314871-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2591628.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1181C>T	p.Thr394Met	missense	Exon 2 of 2	NP_001258942.1	Q8IWB1
	ITPRIP	NM_001272012.2		c.1181C>T	p.Thr394Met	missense	Exon 2 of 2	NP_001258941.1	Q8IWB1
	ITPRIP	NM_033397.4		c.1181C>T	p.Thr394Met	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.1181C>T	p.Thr394Met	missense	Exon 2 of 2	ENSP00000337178.1	Q8IWB1
	ITPRIP	ENST00000278071.6	TSL:1	c.1181C>T	p.Thr394Met	missense	Exon 3 of 3	ENSP00000278071.2	Q8IWB1
	ITPRIP	ENST00000358187.2	TSL:2	c.1181C>T	p.Thr394Met	missense	Exon 2 of 2	ENSP00000350915.2	Q8IWB1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000228 AC: 57 AN: 249766 AF XY: 0.000281

Gnomad AFR exome AF: 0.0000630

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000533

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000161 AC: 235 AN: 1461428 Hom.: 1 Cov.: 34 AF XY: 0.000198 AC XY: 144 AN XY: 727046

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

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

South Asian (SAS) AF: 0.00152 AC: 131 AN: 86258

European-Finnish (FIN) AF: 0.0000944 AC: 5 AN: 52964

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

European-Non Finnish (NFE) AF: 0.0000836 AC: 93 AN: 1112006

Other (OTH) AF: 0.0000828 AC: 5 AN: 60392

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152294 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74468

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000394 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.053
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.9
DANN	Benign	0.45
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.45
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.013
Sift	Benign	0.40	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.053
MVP		0.014
MPC		0.22
ClinPred		0.020	T
GERP RS		-0.15
Varity_R		0.012
gMVP		0.14
Mutation Taster		=100/0	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: rs368032423; hg19: chr10-106074629;