19-16479216-TCG-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_145046.5(CALR3):c.1068_1069delCG(p.Glu357fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
CALR3
NM_145046.5 frameshift
NM_145046.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.57
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CALR3 | NM_145046.5 | c.1068_1069delCG | p.Glu357fs | frameshift_variant | 9/9 | ENST00000269881.8 | NP_659483.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CALR3 | ENST00000269881.8 | c.1068_1069delCG | p.Glu357fs | frameshift_variant | 9/9 | 1 | NM_145046.5 | ENSP00000269881.3 | ||
ENSG00000141979 | ENST00000409035.1 | n.*871_*872delCG | non_coding_transcript_exon_variant | 12/12 | 2 | ENSP00000386951.2 | ||||
ENSG00000141979 | ENST00000409035.1 | n.*871_*872delCG | 3_prime_UTR_variant | 12/12 | 2 | ENSP00000386951.2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461884Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 727240
GnomAD4 exome
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6
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1461884
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5
AN XY:
727240
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GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.