19-5914940-C-G

Variant names:

• chr19-5914940-C-G
• rs61741511
• NM_004058.5:c.262C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004058.5(CAPS):​c.262C>G​(p.Pro88Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000069 in 1,448,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAPS NM_004058.5 missense, splice_region
• Scores: Splicing: ADA: 0.2353
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.94

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]

ENSG00000267314 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPS	NM_004058.5	c.262C>G	p.Pro88Ala	missense_variant, splice_region_variant	Exon 4 of 5	ENST00000588776.8	NP_004049.3
CAPS	NM_080590.4	c.262C>G	p.Pro88Ala	missense_variant, splice_region_variant	Exon 4 of 5		NP_542157.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPS	ENST00000588776.8	c.262C>G	p.Pro88Ala	missense_variant, splice_region_variant	Exon 4 of 5	1	NM_004058.5	ENSP00000465883.2
ENSG00000267314	ENST00000588891.1	n.*556C>G		downstream_gene_variant		4		ENSP00000468419.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000423 AC: 1 AN: 236300 Hom.: 0 AF XY: 0.00000773 AC XY: 1 AN XY: 129412

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 SAS exome AF: 0.0000331

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448888 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 721078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	.;.;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D;T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.34	T
PrimateAI	Uncertain	0.51	T
REVEL	Benign	0.23
Sift4G	Benign	0.11	T;T;D
Vest4		0.64
MutPred		0.32		.;.;Loss of catalytic residue at P88 (P = 0.01);
MVP		0.84
ClinPred		0.94	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.24
dbscSNV1_RF	Benign	0.32
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61741511; hg19: chr19-5914951;