12-53714166-T-G

Variant names:

• chr12-53714166-T-G
• rs1945662274
• NM_020898.3:c.1558A>C

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.1558A>C​(p.Thr520Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T520A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CALCOCO1 NM_020898.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36
• 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=0.10762626).

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.1558A>C	p.Thr520Pro	missense	Exon 12 of 15	NP_065949.1	Q9P1Z2-1
	CALCOCO1	NM_001143682.2		c.1303A>C	p.Thr435Pro	missense	Exon 11 of 14	NP_001137154.1	Q9P1Z2-4
	CALCOCO1	NR_026554.2		n.1528A>C		non_coding_transcript_exon	Exon 11 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCOCO1	ENST00000550804.6	TSL:1 MANE Select	c.1558A>C	p.Thr520Pro	missense	Exon 12 of 15	ENSP00000449960.1	Q9P1Z2-1
	CALCOCO1	ENST00000548263.5	TSL:1	c.1558A>C	p.Thr520Pro	missense	Exon 12 of 14	ENSP00000447647.1	Q9P1Z2-2
	CALCOCO1	ENST00000546443.5	TSL:1	c.106A>C	p.Thr36Pro	missense	Exon 2 of 6	ENSP00000456437.1	H3BRW8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461216 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726976

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60362

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000476 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.4
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.073
Sift	Benign	0.097	T
Sift4G	Uncertain	0.055	T
Polyphen		0.027	B
Vest4		0.20
MutPred		0.54		Loss of stability (P = 0.0753)
MVP		0.28
MPC		0.29
ClinPred		0.11	T
GERP RS		2.6
PromoterAI		-0.035	Neutral
Varity_R		0.069
gMVP		0.23
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1945662274; hg19: chr12-54107950;