NM_020898.3:c.1558A>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020898.3(CALCOCO1):​c.1558A>G​(p.Thr520Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALCOCO1 NM_020898.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0510886).
• BP6: Variant 12-53714166-T-C is Benign according to our data. Variant chr12-53714166-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3136651.Status of the report is criteria_provided_single_submitter, 1 stars.

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>G	p.Thr520Ala	missense	Exon 12 of 15	NP_065949.1	Q9P1Z2-1
	CALCOCO1	NM_001143682.2		c.1303A>G	p.Thr435Ala	missense	Exon 11 of 14	NP_001137154.1	Q9P1Z2-4
	CALCOCO1	NR_026554.2		n.1528A>G		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>G	p.Thr520Ala	missense	Exon 12 of 15	ENSP00000449960.1	Q9P1Z2-1
	CALCOCO1	ENST00000548263.5	TSL:1	c.1558A>G	p.Thr520Ala	missense	Exon 12 of 14	ENSP00000447647.1	Q9P1Z2-2
	CALCOCO1	ENST00000546443.5	TSL:1	c.106A>G	p.Thr36Ala	missense	Exon 2 of 6	ENSP00000456437.1	H3BRW8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.049
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.57
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.2	N
PhyloP100		2.4
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.040
Sift	Benign	0.51	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.48		Loss of glycosylation at T520 (P = 0.08)
MVP		0.13
MPC		0.18
ClinPred		0.040	T
GERP RS		2.6
PromoterAI		-0.0019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.12
Mutation Taster		=96/4	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: rs1945662274; hg19: chr12-54107950;