7-128759009-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001219.5(CALU):āc.554A>Gā(p.Tyr185Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,461,620 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000031 ( 1 hom. )
Consequence
CALU
NM_001219.5 missense
NM_001219.5 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 3.44
Genes affected
CALU (HGNC:1458): (calumenin) The product of this gene is a calcium-binding protein localized in the endoplasmic reticulum (ER) and it is involved in such ER functions as protein folding and sorting. This protein belongs to a family of multiple EF-hand proteins (CERC) that include reticulocalbin, ERC-55, and Cab45 and the product of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38591826).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CALU | NM_001219.5 | c.554A>G | p.Tyr185Cys | missense_variant | 4/7 | ENST00000249364.9 | NP_001210.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CALU | ENST00000249364.9 | c.554A>G | p.Tyr185Cys | missense_variant | 4/7 | 1 | NM_001219.5 | ENSP00000249364 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000757 AC: 19AN: 250944Hom.: 1 AF XY: 0.000103 AC XY: 14AN XY: 135596
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GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461620Hom.: 1 Cov.: 30 AF XY: 0.0000495 AC XY: 36AN XY: 727118
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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13
Asia WGS
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1
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3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2023 | The c.578A>G (p.Y193C) alteration is located in exon 5 (coding exon 4) of the CALU gene. This alteration results from a A to G substitution at nucleotide position 578, causing the tyrosine (Y) at amino acid position 193 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;L;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Uncertain
Sift
Benign
D;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.91
.;.;P;.;.
Vest4
MutPred
Loss of phosphorylation at Y185 (P = 0.0171);.;Loss of phosphorylation at Y185 (P = 0.0171);Loss of phosphorylation at Y185 (P = 0.0171);.;
MVP
MPC
1.2
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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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