NM_005831.5:c.524C>T

Variant names:

• chr17-48849358-C-T
• rs200324523
• NM_005831.5:c.524C>T

Variant summary

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

The NM_005831.5(CALCOCO2):​c.524C>T​(p.Ala175Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,438 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 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: CALCOCO2 NM_005831.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70
• Publications: 0 publications found

Genes affected

CALCOCO2 (HGNC:29912): (calcium binding and coiled-coil domain 2) This gene encodes a coiled-coil domain-containing protein. The encoded protein functions as a receptor for ubiquitin-coated bacteria and plays an important role in innate immunity by mediating macroautophagy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ENSG00000293025 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06351289).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005831.5. 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
	CALCOCO2	NM_005831.5	MANE Select	c.524C>T	p.Ala175Val	missense	Exon 5 of 13	NP_005822.1	Q13137-1
	CALCOCO2	NM_001261390.2		c.596C>T	p.Ala199Val	missense	Exon 6 of 14	NP_001248319.1	Q13137-4
	CALCOCO2	NM_001261391.2		c.587C>T	p.Ala196Val	missense	Exon 6 of 14	NP_001248320.1	Q13137-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCOCO2	ENST00000258947.8	TSL:1 MANE Select	c.524C>T	p.Ala175Val	missense	Exon 5 of 13	ENSP00000258947.3	Q13137-1
	CALCOCO2	ENST00000448105.7	TSL:2	c.596C>T	p.Ala199Val	missense	Exon 6 of 14	ENSP00000398523.2	Q13137-4
	CALCOCO2	ENST00000509507.5	TSL:2	c.587C>T	p.Ala196Val	missense	Exon 6 of 14	ENSP00000424352.1	Q13137-3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250952 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461136 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 726894

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.000179 AC: 8 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5394

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111794

Other (OTH) AF: 0.0000332 AC: 2 AN: 60328

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74480

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.000392 AC: 6 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000576 AC: 7

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	0.085
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0059	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.7
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.10
Sift	Benign	0.13	T
Sift4G	Benign	0.23	T
Polyphen		0.99	D
Vest4		0.20
MVP		0.56
MPC		0.75
ClinPred		0.37	T
GERP RS		4.5
Varity_R		0.10
gMVP		0.097
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs200324523; hg19: chr17-46926720;