10-104314511-C-G

Variant names:

• chr10-104314511-C-G
• NM_001272013.2:c.1541G>C

Variant summary

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

The NM_001272013.2(ITPRIP):​c.1541G>C​(p.Arg514Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITPRIP NM_001272013.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804

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=0.30027008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRIP	NM_001272013.2	c.1541G>C	p.Arg514Pro	missense_variant	Exon 2 of 2	ENST00000337478.3	NP_001258942.1
ITPRIP	NM_001272012.2	c.1541G>C	p.Arg514Pro	missense_variant	Exon 2 of 2		NP_001258941.1
ITPRIP	NM_033397.4	c.1541G>C	p.Arg514Pro	missense_variant	Exon 3 of 3		NP_203755.1
ITPRIP	XM_005270257.3	c.1556G>C	p.Arg519Pro	missense_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.1541G>C	p.Arg514Pro	missense_variant	Exon 2 of 2	1	NM_001272013.2	ENSP00000337178.1
ITPRIP	ENST00000278071.6	c.1541G>C	p.Arg514Pro	missense_variant	Exon 3 of 3	1		ENSP00000278071.2
ITPRIP	ENST00000358187.2	c.1541G>C	p.Arg514Pro	missense_variant	Exon 2 of 2	2		ENSP00000350915.2
ITPRIP	ENST00000647721.1	c.1541G>C	p.Arg514Pro	missense_variant	Exon 3 of 3			ENSP00000497746.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	T;T;T;T
Eigen	Benign	0.052
Eigen_PC	Benign	0.017
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.73	T;.;.;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M;M
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.6	N;N;N;.
REVEL	Benign	0.11
Sift	Benign	0.22	T;T;T;.
Sift4G	Benign	0.19	T;T;T;.
Polyphen		0.91	P;P;P;P
Vest4		0.55
MutPred		0.42		Loss of MoRF binding (P = 0.0059);Loss of MoRF binding (P = 0.0059);Loss of MoRF binding (P = 0.0059);Loss of MoRF binding (P = 0.0059);
MVP		0.21
MPC		0.62
ClinPred		0.85	D
GERP RS		3.2
Varity_R		0.47
gMVP		0.72

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: chr10-106074269;