dbSNP rs375347212: CALCOCO1:p.Glu691Gln (chr12-53711949-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020898.3(CALCOCO1):c.2071G>C(p.Glu691Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000447 in 1,564,578 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 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

CALCOCO1
NM_020898.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Publications

0 publications found

Variant links:

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]

CALCOCO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.2161806).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALCOCO1	NM_020898.3	MANE Select	c.2071G>C	p.Glu691Gln	missense	Exon 15 of 15	NP_065949.1	Q9P1Z2-1
CALCOCO1	NM_001143682.2		c.1816G>C	p.Glu606Gln	missense	Exon 14 of 14	NP_001137154.1	Q9P1Z2-4
CALCOCO1	NR_026554.2		n.2041G>C		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALCOCO1	ENST00000550804.6	TSL:1 MANE Select	c.2071G>C	p.Glu691Gln	missense	Exon 15 of 15	ENSP00000449960.1	Q9P1Z2-1
CALCOCO1	ENST00000546443.5	TSL:1	c.691G>C	p.Glu231Gln	missense	Exon 6 of 6	ENSP00000456437.1	H3BRW8
CALCOCO1	ENST00000548263.5	TSL:1	c.*1147G>C		3_prime_UTR	Exon 14 of 14	ENSP00000447647.1	Q9P1Z2-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

208384

AF XY:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000453

AC:

AN:

1412436

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

697984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31926

American (AMR)

AF:

0.00

AC:

AN:

38076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22324

East Asian (EAS)

AF:

0.00

AC:

AN:

39050

South Asian (SAS)

AF:

0.00

AC:

AN:

77078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.0000533

AC:

AN:

1088656

Other (OTH)

AF:

0.000103

AC:

AN:

58434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

M_CAP

Benign

0.029

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.69

PhyloP100

4.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.1

REVEL

Benign

0.092

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.38

MVP

0.46

MPC

0.73

ClinPred

0.69

GERP RS

3.6

Varity_R

0.29

gMVP

0.29

Mutation Taster

=86/14

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over