Variant 11-65182804-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000279247.11(CAPN1):c.103A>T(p.Ile35Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CAPN1
ENST00000279247.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

CAPN1 (HGNC:1476): (calpain 1) The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 1. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

CAPN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN1	NM_005186.4 linkuse as main transcript	c.103A>T	p.Ile35Phe	missense_variant	2/22	ENST00000279247.11	NP_005177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN1	ENST00000279247.11 linkuse as main transcript	c.103A>T	p.Ile35Phe	missense_variant	2/22	1	NM_005186.4	ENSP00000279247	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1436570

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712372

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:

0.00

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

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

The c.103A>T (p.I35F) alteration is located in exon 2 (coding exon 1) of the CAPN1 gene. This alteration results from a A to T substitution at nucleotide position 103, causing the isoleucine (I) at amino acid position 35 to be replaced by a phenylalanine (F). 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

0.18

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

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

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.53

T;T;.;.;T;.;.;.;D;T;T;T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.48

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

MetaSVM

Uncertain

0.73

MutationAssessor

Uncertain

2.3

.;.;M;.;.;M;M;M;.;.;.;.;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.0

D;D;N;D;D;N;N;N;D;D;D;D;D;N

REVEL

Benign

0.13

Sift

Benign

0.10

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

Sift4G

Benign

0.19

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

Polyphen

0.84

.;.;P;.;.;P;P;P;.;.;.;.;.;P

Vest4

0.28, 0.28, 0.28, 0.22

MutPred

0.46

Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);Gain of methylation at K36 (P = 0.0481);

MVP

0.97

MPC

0.79

ClinPred

0.97

GERP RS

4.9

Varity_R

0.44

gMVP

0.58

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

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