Variant rs61823553 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM1BP4_StrongBA1

The NM_001143962.2(CAPN8):c.1775C>T(p.Thr592Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,550,914 control chromosomes in the GnomAD database, including 213,191 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 17754 hom., cov: 32)

Exomes 𝑓: 0.53 ( 195437 hom. )

Consequence

CAPN8
NM_001143962.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

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 -10 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity CAN8_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=5.6138635E-4).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CAPN8	NM_001143962.2 linkuse as main transcript	c.1775C>T	p.Thr592Met	missense_variant	17/21	ENST00000366872.10
CAPN8	XM_017001265.2 linkuse as main transcript	c.1292C>T	p.Thr431Met	missense_variant	14/18
CAPN8	XM_017001266.2 linkuse as main transcript	c.1094C>T	p.Thr365Met	missense_variant	12/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CAPN8	ENST00000366872.10 linkuse as main transcript	c.1775C>T	p.Thr592Met	missense_variant	17/21	1	NM_001143962.2	P1
CAPN8	ENST00000442247.5 linkuse as main transcript	c.123+4029C>T		intron_variant		5
CAPN8	ENST00000482401.6 linkuse as main transcript	n.86C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70964

AN:

151906

Hom.:

17749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.436

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.475

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.487

GnomAD3 exomes

AF:

0.534

AC:

83565

AN:

156486

Hom.:

22908

AF XY:

0.529

AC XY:

43891

AN XY:

82944

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.617

Gnomad ASJ exome

AF:

0.587

Gnomad EAS exome

AF:

0.527

Gnomad SAS exome

AF:

0.486

Gnomad FIN exome

AF:

0.545

Gnomad NFE exome

AF:

0.545

Gnomad OTH exome

AF:

0.530

GnomAD4 exome

AF:

0.527

AC:

736533

AN:

1398890

Hom.:

195437

Cov.:

AF XY:

0.527

AC XY:

363576

AN XY:

689998

show subpopulations

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.606

Gnomad4 ASJ exome

AF:

0.588

Gnomad4 EAS exome

AF:

0.514

Gnomad4 SAS exome

AF:

0.488

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.534

Gnomad4 OTH exome

AF:

0.506

GnomAD4 genome

AF:

0.467

AC:

71000

AN:

152024

Hom.:

17754

Cov.:

AF XY:

0.469

AC XY:

34819

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.267

Gnomad4 AMR

AF:

0.563

Gnomad4 ASJ

AF:

0.579

Gnomad4 EAS

AF:

0.531

Gnomad4 SAS

AF:

0.476

Gnomad4 FIN

AF:

0.551

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.487

Alfa

AF:

0.513

Hom.:

10533

Bravo

AF:

0.462

TwinsUK

AF:

0.530

AC:

1967

ALSPAC

AF:

0.531

AC:

2047

ESP6500AA

AF:

0.252

AC:

349

ESP6500EA

AF:

0.545

AC:

1733

ExAC

AF:

0.486

AC:

11544

Asia WGS

AF:

0.451

AC:

1569

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

T;T

Eigen

Benign

0.13

Eigen_PC

Benign

-0.041

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.46

T;T

MetaRNN

Benign

0.00056

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.7

.;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.011

.;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.061

MPC

0.0019

ClinPred

0.037

GERP RS

3.5

Varity_R

0.018

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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