Variant chr5-35904605-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001042625.2(CAPSL):c.567C>A(p.Ser189Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CAPSL
NM_001042625.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0320

Variant links:

Genes affected

CAPSL (HGNC:28375): (calcyphosine like) Predicted to enable calcium ion binding activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CAPSL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CAPSL	NM_001042625.2 linkuse as main transcript	c.567C>A	p.Ser189Arg	missense_variant	5/5	ENST00000651391.1
CAPSL	NM_144647.4 linkuse as main transcript	c.567C>A	p.Ser189Arg	missense_variant	5/5
CAPSL	XM_006714444.4 linkuse as main transcript	c.618C>A	p.Ser206Arg	missense_variant	5/5
CAPSL	XM_006714445.4 linkuse as main transcript	c.*91C>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CAPSL	ENST00000651391.1 linkuse as main transcript	c.567C>A	p.Ser189Arg	missense_variant	5/5		NM_001042625.2	P1
CAPSL	ENST00000397367.6 linkuse as main transcript	c.567C>A	p.Ser189Arg	missense_variant	5/5	1		P1
CAPSL	ENST00000397366.5 linkuse as main transcript	c.567C>A	p.Ser189Arg	missense_variant	5/5	3		P1
CAPSL	ENST00000513623.5 linkuse as main transcript	c.567C>A	p.Ser189Arg	missense_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727188

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151810

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74094

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.567C>A (p.S189R) alteration is located in exon 5 (coding exon 4) of the CAPSL gene. This alteration results from a C to A substitution at nucleotide position 567, causing the serine (S) at amino acid position 189 to be replaced by an arginine (R). 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Pathogenic

0.30

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Pathogenic

0.85

MutationAssessor

Pathogenic

3.8

H;H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.87

MutPred

0.56

Loss of glycosylation at S189 (P = 0.1212);Loss of glycosylation at S189 (P = 0.1212);Loss of glycosylation at S189 (P = 0.1212);

MVP

0.41

MPC

0.16

ClinPred

0.97

GERP RS

-8.3

Varity_R

0.85

gMVP

0.95

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over