chr19-5914456-C-A

Variant summary

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

The NM_004058.5(CAPS):​c.50C>A​(p.Ser17Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,612,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

CAPS
NM_004058.5 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.996

Publications

2 publications found
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 was made for transcript

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

BP4
Computational evidence support a benign effect (MetaRNN=0.04656431).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAPSNM_004058.5 linkc.50C>A p.Ser17Tyr missense_variant Exon 2 of 5 ENST00000588776.8 NP_004049.3 Q13938-4A0A384NYV7Q96ET4
CAPSNM_080590.4 linkc.50C>A p.Ser17Tyr missense_variant Exon 2 of 5 NP_542157.3 Q13938

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAPSENST00000588776.8 linkc.50C>A p.Ser17Tyr missense_variant Exon 2 of 5 1 NM_004058.5 ENSP00000465883.2 Q13938-4
ENSG00000267314ENST00000588891.1 linkn.*145C>A non_coding_transcript_exon_variant Exon 3 of 4 4 ENSP00000468419.1 K7ERU9
ENSG00000267314ENST00000588891.1 linkn.*145C>A 3_prime_UTR_variant Exon 3 of 4 4 ENSP00000468419.1 K7ERU9

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152240
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000196
AC:
49
AN:
250314
AF XY:
0.000236
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00199
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000925
Gnomad NFE exome
AF:
0.000177
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000205
AC:
300
AN:
1460298
Hom.:
0
Cov.:
33
AF XY:
0.000211
AC XY:
153
AN XY:
726310
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33466
American (AMR)
AF:
0.000157
AC:
7
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
0.00172
AC:
45
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39682
South Asian (SAS)
AF:
0.000197
AC:
17
AN:
86238
European-Finnish (FIN)
AF:
0.000248
AC:
13
AN:
52410
Middle Eastern (MID)
AF:
0.000693
AC:
4
AN:
5768
European-Non Finnish (NFE)
AF:
0.000184
AC:
204
AN:
1111534
Other (OTH)
AF:
0.000149
AC:
9
AN:
60358
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.487
Heterozygous variant carriers
0
20
40
60
80
100
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152240
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74376
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41458
American (AMR)
AF:
0.00
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00115
AC:
4
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5196
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000191
AC:
13
AN:
68046
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000286
Hom.:
0
Bravo
AF:
0.000159
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000157
AC:
19
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 23, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.50C>A (p.S17Y) alteration is located in exon 2 (coding exon 1) of the CAPS gene. This alteration results from a C to A substitution at nucleotide position 50, causing the serine (S) at amino acid position 17 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.094
.;.;T
Eigen
Benign
-0.032
Eigen_PC
Benign
-0.037
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.61
T;T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.047
T;T;T
MetaSVM
Benign
-0.83
T
PhyloP100
1.0
PrimateAI
Benign
0.38
T
REVEL
Benign
0.16
Sift4G
Uncertain
0.0040
D;D;D
Vest4
0.33
MVP
0.73
ClinPred
0.085
T
GERP RS
2.8
PromoterAI
-0.00070
Neutral
Varity_R
0.13
Mutation Taster
=91/9
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
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

Publications

Other links and lift over

dbSNP: rs139158732; hg19: chr19-5914467; API