ENST00000374316.9:c.-348G>C

Variant names:

• chr6-33621255-G-C
• rs6910386
• ENST00000374316.9:c.-348G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000374316.9(ITPR3):​c.-348G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 144,042 control chromosomes in the GnomAD database, including 62,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.93 (61069 hom., cov: 22)
  • Exomes 𝑓: 0.96 (1144 hom.)
• Consequence: ITPR3 ENST00000374316.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.899
• Publications: 0 publications found

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]

ITPR3 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease, demyelinating, type 1J

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-33621255-G-C is Benign according to our data. Variant chr6-33621255-G-C is described in ClinVar as [Benign]. Clinvar id is 1276370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPR3	NM_002224.4	c.-348G>C		upstream_gene_variant		ENST00000605930.3	NP_002215.2
ITPR3	XM_047418731.1	c.-131G>C		upstream_gene_variant			XP_047274687.1
ITPR3	XM_017010832.2	c.-131G>C		upstream_gene_variant			XP_016866321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPR3	ENST00000374316.9	c.-348G>C		5_prime_UTR_variant	Exon 2 of 59	5		ENSP00000363435.4
ITPR3	ENST00000605930.3	c.-348G>C		upstream_gene_variant		1	NM_002224.4	ENSP00000475177.1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 131240 AN: 141464 Hom.: 61028 Cov.: 22

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.955

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.895

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.916

GnomAD4 exome AF: 0.959 AC: 2380 AN: 2482 Hom.: 1144 Cov.: 0 AF XY: 0.963 AC XY: 1244 AN XY: 1292

African (AFR) AF: 0.815 AC: 101 AN: 124

American (AMR) AF: 0.883 AC: 53 AN: 60

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 75 AN: 80

East Asian (EAS) AF: 0.991 AC: 107 AN: 108

South Asian (SAS) AF: 0.984 AC: 63 AN: 64

European-Finnish (FIN) AF: 0.967 AC: 203 AN: 210

Middle Eastern (MID) AF: 0.950 AC: 19 AN: 20

European-Non Finnish (NFE) AF: 0.968 AC: 1572 AN: 1624

Other (OTH) AF: 0.974 AC: 187 AN: 192

GnomAD4 genome AF: 0.928 AC: 131328 AN: 141560 Hom.: 61069 Cov.: 22 AF XY: 0.930 AC XY: 64306 AN XY: 69148

African (AFR) AF: 0.855 AC: 32943 AN: 38546

American (AMR) AF: 0.955 AC: 13899 AN: 14550

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3185 AN: 3340

East Asian (EAS) AF: 0.980 AC: 4589 AN: 4682

South Asian (SAS) AF: 0.970 AC: 4365 AN: 4498

European-Finnish (FIN) AF: 0.961 AC: 8793 AN: 9150

Middle Eastern (MID) AF: 0.901 AC: 254 AN: 282

European-Non Finnish (NFE) AF: 0.953 AC: 60712 AN: 63710

Other (OTH) AF: 0.917 AC: 1822 AN: 1986

Alfa AF: 0.897 Hom.: 2314

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		0.90
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=190/110	polymorphism

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

Other links and lift over

dbSNP: rs6910386; hg19: chr6-33589032; COSMIC: COSV65414820; COSMIC: COSV65414820;