10-104314774-G-C

Position:

• chr10-104314774-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000337478.3(ITPRIP):​c.1278C>G​(p.Ser426Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITPRIP ENST00000337478.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40355462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPRIP	NM_001272013.2	c.1278C>G	p.Ser426Arg	missense_variant	2/2	ENST00000337478.3	NP_001258942.1
ITPRIP	NM_001272012.2	c.1278C>G	p.Ser426Arg	missense_variant	2/2		NP_001258941.1
ITPRIP	NM_033397.4	c.1278C>G	p.Ser426Arg	missense_variant	3/3		NP_203755.1
ITPRIP	XM_005270257.3	c.1293C>G	p.Ser431Arg	missense_variant	2/2		XP_005270314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPRIP	ENST00000337478.3	c.1278C>G	p.Ser426Arg	missense_variant	2/2	1	NM_001272013.2	ENSP00000337178.1
ITPRIP	ENST00000278071.6	c.1278C>G	p.Ser426Arg	missense_variant	3/3	1		ENSP00000278071.2
ITPRIP	ENST00000358187.2	c.1278C>G	p.Ser426Arg	missense_variant	2/2	2		ENSP00000350915.2
ITPRIP	ENST00000647721.1	c.1278C>G	p.Ser426Arg	missense_variant	3/3			ENSP00000497746.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.1278C>G (p.S426R) alteration is located in exon 3 (coding exon 1) of the ITPRIP gene. This alteration results from a C to G substitution at nucleotide position 1278, causing the serine (S) at amino acid position 426 to be replaced by an arginine (R). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	T;.;.;.
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;M;M
MutationTaster	Benign	0.53	D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.7	N;N;N;.
REVEL	Benign	0.12
Sift	Uncertain	0.011	D;D;D;.
Sift4G	Uncertain	0.0080	D;D;D;.
Polyphen		0.99	D;D;D;D
Vest4		0.44
MutPred		0.38		Gain of methylation at S426 (P = 0.0189);Gain of methylation at S426 (P = 0.0189);Gain of methylation at S426 (P = 0.0189);Gain of methylation at S426 (P = 0.0189);
MVP		0.28
MPC		0.78
ClinPred		0.95	D
GERP RS		1.9
Varity_R		0.23
gMVP		0.34

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: chr10-106074532;