Variant 1-223625884-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001143962.2(CAPN8):c.734C>A(p.Ser245Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,549,168 control chromosomes in the GnomAD database, including 239,331 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 25373 hom., cov: 32)

Exomes 𝑓: 0.55 ( 213958 hom. )

Consequence

CAPN8
NM_001143962.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.00

Variant links:

Genes affected

CAPN8 (HGNC:1485): (calpain 8) Predicted to enable calcium-dependent cysteine-type endopeptidase activity and identical protein binding activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within calcium-dependent self proteolysis. Predicted to be located in Golgi apparatus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CAPN8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.118681E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN8	NM_001143962.2 linkuse as main transcript	c.734C>A	p.Ser245Tyr	missense_variant	6/21	ENST00000366872.10	NP_001137434.1	A6NHC0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN8	ENST00000366872.10 linkuse as main transcript	c.734C>A	p.Ser245Tyr	missense_variant	6/21	1	NM_001143962.2	ENSP00000355837.6		A6NHC0

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86835

AN:

151904

Hom.:

25342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.571

GnomAD3 exomes

AF:

0.556

AC:

87136

AN:

156664

Hom.:

24684

AF XY:

0.562

AC XY:

46642

AN XY:

83002

show subpopulations

Gnomad AFR exome

AF:

0.656

Gnomad AMR exome

AF:

0.528

Gnomad ASJ exome

AF:

0.622

Gnomad EAS exome

AF:

0.622

Gnomad SAS exome

AF:

0.643

Gnomad FIN exome

AF:

0.407

Gnomad NFE exome

AF:

0.543

Gnomad OTH exome

AF:

0.549

GnomAD4 exome

AF:

0.551

AC:

769220

AN:

1397146

Hom.:

213958

Cov.:

AF XY:

0.554

AC XY:

381548

AN XY:

689004

show subpopulations

Gnomad4 AFR exome

AF:

0.648

Gnomad4 AMR exome

AF:

0.528

Gnomad4 ASJ exome

AF:

0.617

Gnomad4 EAS exome

AF:

0.629

Gnomad4 SAS exome

AF:

0.648

Gnomad4 FIN exome

AF:

0.420

Gnomad4 NFE exome

AF:

0.543

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.572

AC:

86923

AN:

152022

Hom.:

25373

Cov.:

AF XY:

0.567

AC XY:

42129

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.655

Gnomad4 AMR

AF:

0.547

Gnomad4 ASJ

AF:

0.606

Gnomad4 EAS

AF:

0.619

Gnomad4 SAS

AF:

0.645

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.542

Gnomad4 OTH

AF:

0.569

Alfa

AF:

0.548

Hom.:

32594

Bravo

AF:

0.583

TwinsUK

AF:

0.528

AC:

1956

ALSPAC

AF:

0.543

AC:

2094

ESP6500AA

AF:

0.663

AC:

918

ESP6500EA

AF:

0.543

AC:

1729

ExAC

AF:

0.561

AC:

13817

Asia WGS

AF:

0.602

AC:

2096

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

T;T;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.00041

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.0

M;.;.

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.027

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.084

MPC

0.0022

ClinPred

0.0095

GERP RS

4.4

Varity_R

0.45

gMVP

0.50

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over