rs2077163

Variant names:

• chr6-33669130-C-A
• NM_002224.4:c.2163C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-33669130-C-A
• chr6-33669130-C-G
• chr6-33669130-C-T

Variant summary

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

The NM_002224.4(ITPR3):​c.2163C>A​(p.His721Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: ITPR3 NM_002224.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

Genes affected

ITPR3 (HGNC:6182): (inositol 1,4,5-trisphosphate receptor type 3) This gene encodes a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. The receptor contains a calcium channel at the C-terminus and the ligand-binding site at the N-terminus. Knockout studies in mice suggest that type 2 and type 3 inositol 1,4,5-trisphosphate receptors play a key role in exocrine secretion underlying energy metabolism and growth. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.2163C>A	p.His721Gln	missense_variant	Exon 18 of 58	ENST00000605930.3	NP_002215.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000605930.3	c.2163C>A	p.His721Gln	missense_variant	Exon 18 of 58	1	NM_002224.4	ENSP00000475177.1
ITPR3	ENST00000374316.9	c.2163C>A	p.His721Gln	missense_variant	Exon 19 of 59	5		ENSP00000363435.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461682 Hom.: 0 Cov.: 54 AF XY: 0.00000138 AC XY: 1 AN XY: 727146

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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	1.9
DANN	Benign	0.95
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.27	N;.
REVEL	Uncertain	0.53
Sift	Benign	0.23	T;.
Sift4G	Benign	0.23	T;T
Polyphen		0.36	B;B
Vest4		0.58
MutPred		0.21		Loss of catalytic residue at H721 (P = 0.0542);Loss of catalytic residue at H721 (P = 0.0542);
MVP		0.89
MPC		0.67
ClinPred		0.35	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.19

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: chr6-33636907;