Variant 11-77084939-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004055.5(CAPN5):c.53G>A(p.Arg18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000806 in 1,613,954 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R18W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00049 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 13 hom. )

Consequence

CAPN5
NM_004055.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.35

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048600137).

BP6

Variant 11-77084939-G-A is Benign according to our data. Variant chr11-77084939-G-A is described in ClinVar as [Benign]. Clinvar id is 1167001.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-77084939-G-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 75 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CAPN5	NM_004055.5 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	2/13	ENST00000648180.1	NP_004046.2
CAPN5	XM_011545225.1 linkuse as main transcript	c.173G>A	p.Arg58Gln	missense_variant	3/14		XP_011543527.1
CAPN5	XM_017018223.3 linkuse as main transcript	c.161G>A	p.Arg54Gln	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.53G>A	p.Arg18Gln	missense_variant	2/13		NM_004055.5	ENSP00000498132	P1

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00155

AC:

389

AN:

250936

Hom.:

AF XY:

0.00213

AC XY:

289

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000839

AC:

1226

AN:

1461620

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

827

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00287

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000492

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000337

Hom.:

Bravo

AF:

0.000268

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000699

AC:

ExAC

AF:

0.00163

AC:

198

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.076

T;T;T;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.89

.;D;.;D;D

MetaRNN

Benign

0.0049

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

N;.;N;N;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.20

N;N;.;N;N

REVEL

Benign

0.083

Sift

Benign

0.58

T;T;.;T;T

Sift4G

Benign

0.29

T;T;.;T;T

Polyphen

0.88

P;.;P;P;B

Vest4

0.45

MVP

0.40

MPC

0.32

ClinPred

0.040

GERP RS

4.1

Varity_R

0.056

gMVP

0.36

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