chr12-53713815-G-C

Variant names:

• chr12-53713815-G-C
• rs202198086
• NM_020898.3:c.1677C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020898.3(CALCOCO1):​c.1677C>G​(p.Asp559Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000971 in 1,575,750 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D559N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000096 (1 hom.)
• Consequence: CALCOCO1 NM_020898.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.657
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026361108).

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.1677C>G	p.Asp559Glu	missense	Exon 13 of 15	NP_065949.1	Q9P1Z2-1
	CALCOCO1	NM_001143682.2		c.1422C>G	p.Asp474Glu	missense	Exon 12 of 14	NP_001137154.1	Q9P1Z2-4
	CALCOCO1	NR_026554.2		n.1647C>G		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.1677C>G	p.Asp559Glu	missense	Exon 13 of 15	ENSP00000449960.1	Q9P1Z2-1
	CALCOCO1	ENST00000548263.5	TSL:1	c.1677C>G	p.Asp559Glu	missense	Exon 13 of 14	ENSP00000447647.1	Q9P1Z2-2
	CALCOCO1	ENST00000546443.5	TSL:1	c.225C>G	p.Asp75Glu	missense	Exon 3 of 6	ENSP00000456437.1	H3BRW8

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152180 Hom.: 0 Cov.: 32

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: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000160 AC: 34 AN: 213160 AF XY: 0.000114

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000255

Gnomad NFE exome AF: 0.000284

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000955 AC: 136 AN: 1423570 Hom.: 1 Cov.: 31 AF XY: 0.0000708 AC XY: 50 AN XY: 706316

African (AFR) AF: 0.00 AC: 0 AN: 31780

American (AMR) AF: 0.00 AC: 0 AN: 37056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23326

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.000125 AC: 10 AN: 79998

European-Finnish (FIN) AF: 0.000326 AC: 17 AN: 52128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.0000986 AC: 108 AN: 1095712

Other (OTH) AF: 0.0000171 AC: 1 AN: 58624

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.000181 AC: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.020
DANN	Benign	0.21
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.66
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.0090
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.066	B
Vest4		0.24
MutPred		0.29		Gain of catalytic residue at L554 (P = 0.0035)
MVP		0.072
MPC		0.17
ClinPred		0.018	T
GERP RS		0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.032
gMVP		0.095
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs202198086; hg19: chr12-54107599;