19-5914940-C-G

Variant summary

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

The NM_004058.5(CAPS):ā€‹c.262C>Gā€‹(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 š‘“: 6.9e-7 ( 0 hom. )

Consequence

CAPS
NM_004058.5 missense, splice_region

Scores

7
9
Splicing: ADA: 0.2353
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.94
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
CAPSNM_004058.5 linkc.262C>G p.Pro88Ala missense_variant, splice_region_variant Exon 4 of 5 ENST00000588776.8 NP_004049.3 Q13938-4A0A384NYV7Q96ET4
CAPSNM_080590.4 linkc.262C>G p.Pro88Ala missense_variant, splice_region_variant Exon 4 of 5 NP_542157.3 Q13938

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAPSENST00000588776.8 linkc.262C>G p.Pro88Ala missense_variant, splice_region_variant Exon 4 of 5 1 NM_004058.5 ENSP00000465883.2 Q13938-4

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
show subpopulations
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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61741511; hg19: chr19-5914951; API