chr12-53714166-T-C

Position:

• chr12-53714166-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020898.3(CALCOCO1):​c.1558A>G​(p.Thr520Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALCOCO1 NM_020898.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.36

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]

CALCOCO1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0510886).
• BP6: Variant 12-53714166-T-C is Benign according to our data. Variant chr12-53714166-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3136651.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCOCO1	NM_020898.3	c.1558A>G	p.Thr520Ala	missense_variant	12/15	ENST00000550804.6	NP_065949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCOCO1	ENST00000550804.6	c.1558A>G	p.Thr520Ala	missense_variant	12/15	1	NM_020898.3	ENSP00000449960.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.57
DEOGEN2	Benign	0.0085	.;.;.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.41	T;T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.051	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.2	N;.;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.44	N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.51	T;T;T;T
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.11
MutPred		0.48		Loss of glycosylation at T520 (P = 0.08);.;Loss of glycosylation at T520 (P = 0.08);Loss of glycosylation at T520 (P = 0.08);
MVP		0.13
MPC		0.18
ClinPred		0.040	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-54107950;