Genetic Variant CAPS:p.Pro88Ser (chr19-5914940-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_004058.5(CAPS):c.262C>T(p.Pro88Ser) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P88T) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CAPS
NM_004058.5 missense, splice_region

Scores

Splicing: ADA: 0.7842

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.94

Publications

3 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]

CAPS links:

ENSG00000267571 (HGNC:):

ENSG00000267571 links:

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ACMG classification

Classification was made for transcript

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.262C>T	p.Pro88Ser	missense splice_region	Exon 4 of 5	NP_004049.3	Q13938-4
	CAPS	NM_080590.4		c.262C>T	p.Pro88Ser	missense splice_region	Exon 4 of 5	NP_542157.3	A0A499FJ41

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAPS	ENST00000588776.8	TSL:1 MANE Select	c.262C>T	p.Pro88Ser	missense splice_region	Exon 4 of 5	ENSP00000465883.2	Q13938-4
CAPS	ENST00000585541.1	TSL:1	n.594C>T		non_coding_transcript_exon	Exon 2 of 2
CAPS	ENST00000961097.1		c.262C>T	p.Pro88Ser	missense splice_region	Exon 4 of 5	ENSP00000631156.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1448888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721078

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25868

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

85832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44020

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5268

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110040

Other (OTH)

AF:

0.00

AC:

AN:

60156

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.48

MetaSVM

Uncertain

-0.25

PhyloP100

6.9

PrimateAI

Uncertain

0.52

REVEL

Benign

0.26

Sift4G

Uncertain

0.020

Vest4

0.64

MutPred

0.31

Loss of catalytic residue at P88 (P = 0.0036)

MVP

0.85

ClinPred

1.0

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.57

Mutation Taster

=40/60

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.78

dbscSNV1_RF

Benign

0.65

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over