rs149634686
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_145046.5(CALR3):āc.125A>Gā(p.Asn42Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000231 in 1,614,076 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. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0011 ( 0 hom., cov: 32)
Exomes š: 0.00014 ( 0 hom. )
Consequence
CALR3
NM_145046.5 missense
NM_145046.5 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 4.72
Genes affected
CALR3 (HGNC:20407): (calreticulin 3) The protein encoded by this gene belongs to the calreticulin family, members of which are calcium-binding chaperones localized mainly in the endoplasmic reticulum. This protein is also localized to the endoplasmic reticulum lumen, however, its capacity for calcium-binding may be absent or much lower than other family members. This gene is specifically expressed in the testis, and may be required for sperm fertility. Mutation in this gene has been associated with familial hypertrophic cardiomyopathy. [provided by RefSeq, Dec 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.005948633).
BP6
?
Variant 19-16495819-T-C is Benign according to our data. Variant chr19-16495819-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 241949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-16495819-T-C is described in Lovd as [Benign]. Variant chr19-16495819-T-C is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd4 at 170 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALR3 | NM_145046.5 | c.125A>G | p.Asn42Ser | missense_variant | 2/9 | ENST00000269881.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALR3 | ENST00000269881.8 | c.125A>G | p.Asn42Ser | missense_variant | 2/9 | 1 | NM_145046.5 | P1 | |
CALR3 | ENST00000600762.1 | c.116A>G | p.Asn39Ser | missense_variant | 2/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00112 AC: 170AN: 152094Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
170
AN:
152094
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000350 AC: 88AN: 251468Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135920
GnomAD3 exomes
AF:
AC:
88
AN:
251468
Hom.:
AF XY:
AC XY:
26
AN XY:
135920
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000139 AC: 203AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 84AN XY: 727232
GnomAD4 exome
AF:
AC:
203
AN:
1461864
Hom.:
Cov.:
31
AF XY:
AC XY:
84
AN XY:
727232
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00112 AC: 170AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.00109 AC XY: 81AN XY: 74418
GnomAD4 genome
?
AF:
AC:
170
AN:
152212
Hom.:
Cov.:
32
AF XY:
AC XY:
81
AN XY:
74418
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
18
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
51
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypertrophic cardiomyopathy 19 Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Sep 08, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 26, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
CALR3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 24, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at