Variant chr19-36141058-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001749.4(CAPNS1):c.47G>C(p.Gly16Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,378,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CAPNS1
NM_001749.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

CAPNS1 (HGNC:1481): (calpain small subunit 1) This gene is a member of the calpain small subunit family. Calpains are calcium-dependent cysteine proteinases that are widely distributed in mammalian cells. Calpains operate as heterodimers, comprising a specific large catalytic subunit (calpain 1 subunit in Calpain I, and calpain 2 subunit in Calpain II), and a common small regulatory subunit encoded by this gene. This encoded protein is essential for the stability and function of both calpain heterodimers, whose proteolytic activities influence various cellular functions including apoptosis, proliferation, migration, adhesion, and autophagy. Calpains have been implicated in neurodegenerative processes, such as myotonic dystrophy. A pseudogene of this gene has been defined on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

CAPNS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28446007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPNS1	NM_001749.4 linkuse as main transcript	c.47G>C	p.Gly16Ala	missense_variant	2/11	ENST00000246533.8	NP_001740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPNS1	ENST00000246533.8 linkuse as main transcript	c.47G>C	p.Gly16Ala	missense_variant	2/11	1	NM_001749.4	ENSP00000246533	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1378416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682018

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:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 05, 2023

The c.47G>C (p.G16A) alteration is located in exon 2 (coding exon 1) of the CAPNS1 gene. This alteration results from a G to C substitution at nucleotide position 47, causing the glycine (G) at amino acid position 16 to be replaced by an alanine (A). 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

0.10

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.22

T;T;T;T;.;T;T;T;.;T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

.;.;T;T;T;T;.;T;T;.;T

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.28

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.55

N;.;.;.;.;.;.;N;.;.;.

MutationTaster

Benign

0.99

N;N;N;N;N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.26

N;.;.;.;.;.;.;.;.;.;.

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;.;.;.;.;.;.;.;.;.;.

Sift4G

Uncertain

0.047

D;T;T;D;D;D;T;D;D;D;T

Polyphen

0.0

B;.;.;.;.;.;.;B;.;.;.

Vest4

0.46

MutPred

0.30

Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.87

MPC

1.2

ClinPred

0.50

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.23

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over