NM_001272013.2:c.901A>C

Variant names:

• chr10-104315151-T-G
• rs1322589782
• NM_001272013.2:c.901A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001272013.2(ITPRIP):​c.901A>C​(p.Met301Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0000014 (0 hom.)
• Consequence: ITPRIP NM_001272013.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21329647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRIP	NM_001272013.2	c.901A>C	p.Met301Leu	missense_variant	Exon 2 of 2	ENST00000337478.3	NP_001258942.1
ITPRIP	NM_001272012.2	c.901A>C	p.Met301Leu	missense_variant	Exon 2 of 2		NP_001258941.1
ITPRIP	NM_033397.4	c.901A>C	p.Met301Leu	missense_variant	Exon 3 of 3		NP_203755.1
ITPRIP	XM_005270257.3	c.916A>C	p.Met306Leu	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.901A>C	p.Met301Leu	missense_variant	Exon 2 of 2	1	NM_001272013.2	ENSP00000337178.1
ITPRIP	ENST00000278071.6	c.901A>C	p.Met301Leu	missense_variant	Exon 3 of 3	1		ENSP00000278071.2
ITPRIP	ENST00000358187.2	c.901A>C	p.Met301Leu	missense_variant	Exon 2 of 2	2		ENSP00000350915.2
ITPRIP	ENST00000647721.1	c.901A>C	p.Met301Leu	missense_variant	Exon 3 of 3			ENSP00000497746.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251020 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135726

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461820 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

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	Benign	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.12	T;T;T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.69	T;.;.;.
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.78	N;N;N;.
REVEL	Benign	0.068
Sift	Benign	0.24	T;T;T;.
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		0.0080	B;B;B;B
Vest4		0.29
MutPred		0.52		Gain of methylation at K302 (P = 0.0334);Gain of methylation at K302 (P = 0.0334);Gain of methylation at K302 (P = 0.0334);Gain of methylation at K302 (P = 0.0334);
MVP		0.030
MPC		0.21
ClinPred		0.47	T
GERP RS		4.3
Varity_R		0.26
gMVP		0.46

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: rs1322589782; hg19: chr10-106074909;