rs1353443967

Variant names:

• chr17-48849375-C-A
• rs1353443967
• NM_005831.5:c.541C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-48849375-C-A
• chr17-48849375-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005831.5(CALCOCO2):​c.541C>A​(p.Gln181Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000377 in 1,460,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q181H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: CALCOCO2 NM_005831.5 missense, splice_region
• Scores: Splicing: ADA: 0.1834
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38
• Publications: 1 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: 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=0.15142342).

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.541C>A	p.Gln181Lys	missense splice_region	Exon 5 of 13	NP_005822.1	Q13137-1
	CALCOCO2	NM_001261390.2		c.613C>A	p.Gln205Lys	missense splice_region	Exon 6 of 14	NP_001248319.1	Q13137-4
	CALCOCO2	NM_001261391.2		c.604C>A	p.Gln202Lys	missense splice_region	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.541C>A	p.Gln181Lys	missense splice_region	Exon 5 of 13	ENSP00000258947.3	Q13137-1
	CALCOCO2	ENST00000448105.7	TSL:2	c.613C>A	p.Gln205Lys	missense splice_region	Exon 6 of 14	ENSP00000398523.2	Q13137-4
	CALCOCO2	ENST00000509507.5	TSL:2	c.604C>A	p.Gln202Lys	missense splice_region	Exon 6 of 14	ENSP00000424352.1	Q13137-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250598 AF XY: 0.00000738

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: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000377 AC: 55 AN: 1460436 Hom.: 0 Cov.: 31 AF XY: 0.0000317 AC XY: 23 AN XY: 726568

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5114

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111552

Other (OTH) AF: 0.00 AC: 0 AN: 60286

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.081
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00065	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.038
Sift	Benign	0.18	T
Sift4G	Benign	0.56	T
Polyphen		0.069	B
Vest4		0.32
MutPred		0.46		Gain of ubiquitination at Q181 (P = 0.009)
MVP		0.51
MPC		0.86
ClinPred		0.56	D
GERP RS		5.0
Varity_R		0.071
gMVP		0.25
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.18
dbscSNV1_RF	Benign	0.40
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: rs1353443967; hg19: chr17-46926737;