6-33621255-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.899

Publications

0 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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
ITPR3NM_002224.4 linkc.-348G>C upstream_gene_variant ENST00000605930.3 NP_002215.2 Q14573A6H8K3Q59ES2
ITPR3XM_047418731.1 linkc.-131G>C upstream_gene_variant XP_047274687.1
ITPR3XM_017010832.2 linkc.-131G>C upstream_gene_variant XP_016866321.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITPR3ENST00000374316.9 linkc.-348G>C 5_prime_UTR_variant Exon 2 of 59 5 ENSP00000363435.4 Q14573
ITPR3ENST00000605930.3 linkc.-348G>C upstream_gene_variant 1 NM_002224.4 ENSP00000475177.1 Q14573

Frequencies

GnomAD3 genomes
AF:
0.928
AC:
131240
AN:
141464
Hom.:
61028
Cov.:
22
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.519
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.928
AC:
131328
AN:
141560
Hom.:
61069
Cov.:
22
AF XY:
0.930
AC XY:
64306
AN XY:
69148
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.563
Heterozygous variant carriers
0
408
816
1223
1631
2039
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
826
1652
2478
3304
4130
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.897
Hom.:
2314

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

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

Publications

Other links and lift over

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