CALCOCO1 p.Gly646Arg

Variant names:

• chr12-53712084-C-G
• NM_020898.3:c.1936G>C
• CALCOCO1 p.Gly646Arg

Your query was ambiguous. Multiple possible variants found:

• chr12-53712084-C-G
• chr12-53712084-C-T
• chr12-53712082-CCC-ACG
• chr12-53712082-CCC-GCG
• chr12-53712082-CCC-TCG
• chr12-53712082-CCC-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020898.3(CALCOCO1):​c.1936G>C​(p.Gly646Arg) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALCOCO1 NM_020898.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18245435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020898.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCOCO1	NM_020898.3	MANE Select	c.1936G>C	p.Gly646Arg	missense	Exon 15 of 15	NP_065949.1	Q9P1Z2-1
	CALCOCO1	NM_001143682.2		c.1681G>C	p.Gly561Arg	missense	Exon 14 of 14	NP_001137154.1	Q9P1Z2-4
	CALCOCO1	NR_026554.2		n.1906G>C		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCOCO1	ENST00000550804.6	TSL:1 MANE Select	c.1936G>C	p.Gly646Arg	missense	Exon 15 of 15	ENSP00000449960.1	Q9P1Z2-1
	CALCOCO1	ENST00000546443.5	TSL:1	c.556G>C	p.Gly186Arg	missense	Exon 6 of 6	ENSP00000456437.1	H3BRW8
	CALCOCO1	ENST00000548263.5	TSL:1	c.*1012G>C		3_prime_UTR	Exon 14 of 14	ENSP00000447647.1	Q9P1Z2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.0036
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.12
Sift	Benign	0.052	T
Sift4G	Benign	0.10	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.21
Mutation Taster		=71/29	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-54105868;