NM_004058.5:c.280C>G

Variant names:

• chr19-5914958-C-G
• rs768276521
• NM_004058.5:c.280C>G

Variant summary

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

The NM_004058.5(CAPS):​c.280C>G​(p.Arg94Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAPS NM_004058.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.764
• Publications: 0 publications found

Genes affected

CAPS (HGNC:1487): (calcyphosine) This gene encodes a calcium-binding protein, which may play a role in the regulation of ion transport. A similar protein was first described as a potentially important regulatory protein in the dog thyroid and was termed as R2D5 antigen in rabbit. Alternative splicing of this gene generates two transcript variants. [provided by RefSeq, Jul 2008]

ENSG00000267571 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004058.5. 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
	CAPS	NM_004058.5	MANE Select	c.280C>G	p.Arg94Gly	missense	Exon 4 of 5	NP_004049.3	Q13938-4
	CAPS	NM_080590.4		c.280C>G	p.Arg94Gly	missense	Exon 4 of 5	NP_542157.3	A0A499FJ41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPS	ENST00000588776.8	TSL:1 MANE Select	c.280C>G	p.Arg94Gly	missense	Exon 4 of 5	ENSP00000465883.2	Q13938-4
	CAPS	ENST00000585541.1	TSL:1	n.612C>G		non_coding_transcript_exon	Exon 2 of 2
	CAPS	ENST00000961097.1		c.280C>G	p.Arg94Gly	missense	Exon 4 of 5	ENSP00000631156.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

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	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.36	D
PhyloP100		0.76
PrimateAI	Uncertain	0.51	T
REVEL	Uncertain	0.29
Sift4G	Uncertain	0.0040	D
Vest4		0.85
MutPred		0.51		Loss of stability (P = 0.0657)
MVP		0.86
ClinPred		1.0	D
GERP RS		2.7
Varity_R		0.45
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs768276521; hg19: chr19-5914969;