Variant 11-77084916-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004055.5(CAPN5):c.30C>G(p.Asp10Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,614,030 control chromosomes in the GnomAD database, including 333 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 177 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 156 hom. )

Consequence

CAPN5
NM_004055.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.182

Variant links:

Genes affected

CAPN5 (HGNC:1482): (calpain 5) Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]

CAPN5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016339123).

BP6

Variant 11-77084916-C-G is Benign according to our data. Variant chr11-77084916-C-G is described in ClinVar as [Benign]. Clinvar id is 259224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CAPN5	NM_004055.5 linkuse as main transcript	c.30C>G	p.Asp10Glu	missense_variant	2/13	ENST00000648180.1	NP_004046.2
CAPN5	XM_011545225.1 linkuse as main transcript	c.150C>G	p.Asp50Glu	missense_variant	3/14		XP_011543527.1
CAPN5	XM_017018223.3 linkuse as main transcript	c.138C>G	p.Asp46Glu	missense_variant	2/13		XP_016873712.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN5	ENST00000648180.1 linkuse as main transcript	c.30C>G	p.Asp10Glu	missense_variant	2/13		NM_004055.5	ENSP00000498132	P1

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3816

AN:

152162

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0878

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00889

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:

0.000191

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.00624

AC:

1568

AN:

251194

Hom.:

AF XY:

0.00455

AC XY:

618

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0866

Gnomad AMR exome

AF:

0.00347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00266

AC:

3889

AN:

1461750

Hom.:

156

Cov.:

AF XY:

0.00225

AC XY:

1635

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0953

Gnomad4 AMR exome

AF:

0.00411

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.00543

GnomAD4 genome

AF:

0.0251

AC:

3825

AN:

152280

Hom.:

177

Cov.:

AF XY:

0.0244

AC XY:

1816

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0877

Gnomad4 AMR

AF:

0.00888

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00238

Hom.:

Bravo

AF:

0.0287

ESP6500AA

AF:

0.0918

AC:

404

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00783

AC:

950

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

T;T;T;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.74

.;T;.;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;L;L;.

MutationTaster

Benign

0.63

D;D;D;D

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;N;.;N;N

REVEL

Benign

0.034

Sift

Benign

0.071

T;T;.;T;T

Sift4G

Benign

0.29

T;T;.;T;T

Polyphen

0.0

B;.;B;B;B

Vest4

0.15

MutPred

0.37

Gain of ubiquitination at K6 (P = 0.07);Gain of ubiquitination at K6 (P = 0.07);Gain of ubiquitination at K6 (P = 0.07);Gain of ubiquitination at K6 (P = 0.07);Gain of ubiquitination at K6 (P = 0.07);

MVP

0.44

MPC

0.14

ClinPred

0.013

GERP RS

3.3

Varity_R

0.082

gMVP

0.28

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