12-53713878-G-C

Variant names:

• chr12-53713878-G-C
• rs140431811
• NM_020898.3:c.1614C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020898.3(CALCOCO1):​c.1614C>G​(p.Asp538Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000905 in 1,524,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000085 (0 hom.)
• Consequence: CALCOCO1 NM_020898.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.41
• Publications: 2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0932796).

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.1614C>G	p.Asp538Glu	missense	Exon 13 of 15	NP_065949.1	Q9P1Z2-1
	CALCOCO1	NM_001143682.2		c.1359C>G	p.Asp453Glu	missense	Exon 12 of 14	NP_001137154.1	Q9P1Z2-4
	CALCOCO1	NR_026554.2		n.1584C>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.1614C>G	p.Asp538Glu	missense	Exon 13 of 15	ENSP00000449960.1	Q9P1Z2-1
	CALCOCO1	ENST00000548263.5	TSL:1	c.1614C>G	p.Asp538Glu	missense	Exon 13 of 14	ENSP00000447647.1	Q9P1Z2-2
	CALCOCO1	ENST00000546443.5	TSL:1	c.162C>G	p.Asp54Glu	missense	Exon 3 of 6	ENSP00000456437.1	H3BRW8

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000131 AC: 24 AN: 182910 AF XY: 0.000135

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00124

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.000479

GnomAD4 exome AF: 0.0000845 AC: 116 AN: 1372664 Hom.: 0 Cov.: 31 AF XY: 0.0000861 AC XY: 58 AN XY: 673286

African (AFR) AF: 0.00 AC: 0 AN: 30476

American (AMR) AF: 0.00 AC: 0 AN: 30944

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 33 AN: 20446

East Asian (EAS) AF: 0.00 AC: 0 AN: 38864

South Asian (SAS) AF: 0.00 AC: 0 AN: 71566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5348

European-Non Finnish (NFE) AF: 0.0000702 AC: 75 AN: 1068584

Other (OTH) AF: 0.000142 AC: 8 AN: 56406

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68020

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

Alfa AF: 0.000159 Hom.: 1

Bravo AF: 0.000132

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000116 AC: 14

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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.16
Sift	Benign	0.061	T
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.49		Gain of glycosylation at T537 (P = 0.1659)
MVP		0.60
MPC		0.71
ClinPred		0.13	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.26
Mutation Taster		=72/28	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: rs140431811; hg19: chr12-54107662;