NM_020898.3:c.1703G>T

Variant names:

• chr12-53713789-C-A
• rs763755443
• NM_020898.3:c.1703G>T

Variant summary

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

The NM_020898.3(CALCOCO1):​c.1703G>T​(p.Arg568Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,394 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R568Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CALCOCO1 NM_020898.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1703G>T	p.Arg568Leu	missense	Exon 13 of 15	NP_065949.1	Q9P1Z2-1
	CALCOCO1	NM_001143682.2		c.1448G>T	p.Arg483Leu	missense	Exon 12 of 14	NP_001137154.1	Q9P1Z2-4
	CALCOCO1	NR_026554.2		n.1673G>T		non_coding_transcript_exon	Exon 12 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCOCO1	ENST00000550804.6	TSL:1 MANE Select	c.1703G>T	p.Arg568Leu	missense	Exon 13 of 15	ENSP00000449960.1	Q9P1Z2-1
	CALCOCO1	ENST00000548263.5	TSL:1	c.1703G>T	p.Arg568Leu	missense	Exon 13 of 14	ENSP00000447647.1	Q9P1Z2-2
	CALCOCO1	ENST00000546443.5	TSL:1	c.251G>T	p.Arg84Leu	missense	Exon 3 of 6	ENSP00000456437.1	H3BRW8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450394 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721136

African (AFR) AF: 0.00 AC: 0 AN: 33054

American (AMR) AF: 0.00 AC: 0 AN: 42826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25436

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39496

South Asian (SAS) AF: 0.00 AC: 0 AN: 84682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106412

Other (OTH) AF: 0.00 AC: 0 AN: 59782

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.70
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.18
Sift	Benign	0.21	T
Sift4G	Benign	0.17	T
Polyphen		0.99	D
Vest4		0.63
MutPred		0.48		Gain of catalytic residue at L573 (P = 0.017)
MVP		0.46
MPC		0.37
ClinPred		0.81	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs763755443; hg19: chr12-54107573;