12-53713837-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020898.3(CALCOCO1):ā€‹c.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

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65
Variant links:
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]

Genome browser will be placed here

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
CALCOCO1NM_020898.3 linkuse as main transcriptc.1655A>C p.Tyr552Ser missense_variant 13/15 ENST00000550804.6 NP_065949.1 Q9P1Z2-1A0A024RAZ1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CALCOCO1ENST00000550804.6 linkuse as main transcriptc.1655A>C p.Tyr552Ser missense_variant 13/151 NM_020898.3 ENSP00000449960.1 Q9P1Z2-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152020
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1400080
Hom.:
0
Cov.:
31
AF XY:
0.00000289
AC XY:
2
AN XY:
691126
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152020
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsAug 07, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Uncertain
0.014
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.16
.;.;.;T
Eigen
Benign
0.059
Eigen_PC
Benign
0.068
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.84
T;T;T;T
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.63
D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;.;L;L
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-2.4
N;D;N;D
REVEL
Benign
0.17
Sift
Benign
0.045
D;D;D;T
Sift4G
Uncertain
0.039
D;T;D;D
Polyphen
0.76
P;.;P;P
Vest4
0.70
MutPred
0.42
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
0.37
MPC
0.79
ClinPred
0.86
D
GERP RS
3.9
Varity_R
0.19
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747381370; hg19: chr12-54107621; API