12-53713837-T-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020898.3(CALCOCO1):āc.1655A>Cā(p.Tyr552Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000193 in 1,552,100 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
CALCOCO1
NM_020898.3 missense
NM_020898.3 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 3.65
Genes affected
CALCOCO1 (HGNC:29306): (calcium binding and coiled-coil domain 1) Enables several functions, including armadillo repeat domain binding activity; beta-catenin binding activity; and nuclear receptor coactivator activity. Involved in positive regulation of gene expression and positive regulation of transcription, DNA-templated. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CALCOCO1 | NM_020898.3 | c.1655A>C | p.Tyr552Ser | missense_variant | 13/15 | ENST00000550804.6 | NP_065949.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CALCOCO1 | ENST00000550804.6 | c.1655A>C | p.Tyr552Ser | missense_variant | 13/15 | 1 | NM_020898.3 | ENSP00000449960.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152020Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000143 AC: 2AN: 1400080Hom.: 0 Cov.: 31 AF XY: 0.00000289 AC XY: 2AN XY: 691126
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152020Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74254
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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 | Aug 07, 2024 | The c.1655A>C (p.Y552S) alteration is located in exon 13 (coding exon 12) of the CALCOCO1 gene. This alteration results from a A to C substitution at nucleotide position 1655, causing the tyrosine (Y) at amino acid position 552 to be replaced by a serine (S). 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;D;N;D
REVEL
Benign
Sift
Benign
D;D;D;T
Sift4G
Uncertain
D;T;D;D
Polyphen
P;.;P;P
Vest4
MutPred
Gain of catalytic residue at P550 (P = 0.0028);.;Gain of catalytic residue at P550 (P = 0.0028);Gain of catalytic residue at P550 (P = 0.0028);
MVP
MPC
0.79
ClinPred
D
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gMVP
Splicing
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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