10-104314542-G-T

Variant names:

• chr10-104314542-G-T
• rs756456665
• NM_001272013.2:c.1510C>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001272013.2(ITPRIP):​c.1510C>A​(p.Arg504Arg) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITPRIP NM_001272013.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=2.51 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRIP	NM_001272013.2	c.1510C>A	p.Arg504Arg	synonymous_variant	Exon 2 of 2	ENST00000337478.3	NP_001258942.1
ITPRIP	NM_001272012.2	c.1510C>A	p.Arg504Arg	synonymous_variant	Exon 2 of 2		NP_001258941.1
ITPRIP	NM_033397.4	c.1510C>A	p.Arg504Arg	synonymous_variant	Exon 3 of 3		NP_203755.1
ITPRIP	XM_005270257.3	c.1525C>A	p.Arg509Arg	synonymous_variant	Exon 2 of 2		XP_005270314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPRIP	ENST00000337478.3	c.1510C>A	p.Arg504Arg	synonymous_variant	Exon 2 of 2	1	NM_001272013.2	ENSP00000337178.1
ITPRIP	ENST00000278071.6	c.1510C>A	p.Arg504Arg	synonymous_variant	Exon 3 of 3	1		ENSP00000278071.2
ITPRIP	ENST00000358187.2	c.1510C>A	p.Arg504Arg	synonymous_variant	Exon 2 of 2	2		ENSP00000350915.2
ITPRIP	ENST00000647721.1	c.1510C>A	p.Arg504Arg	synonymous_variant	Exon 3 of 3			ENSP00000497746.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.3
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs756456665; hg19: chr10-106074300;