rs1473867213

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023083.4(CAPN10):c.8C>A(p.Ala3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,276,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

CAPN10
NM_023083.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.924

Publications

0 publications found

Variant links:

Genes affected

CAPN10 (HGNC:1477): (calpain 10) Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene. [provided by RefSeq, Sep 2010]

CAPN10 links:

CAPN10-DT (HGNC:48839): (CAPN10 divergent transcript)

CAPN10-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2496475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023083.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN10	NM_023083.4	MANE Select	c.8C>A	p.Ala3Glu	missense	Exon 1 of 12	NP_075571.2	Q9HC96-1
	CAPN10	NM_023085.4		c.8C>A	p.Ala3Glu	missense	Exon 1 of 10	NP_075573.3	Q9HC96-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAPN10	ENST00000391984.7	TSL:1 MANE Select	c.8C>A	p.Ala3Glu	missense	Exon 1 of 12	ENSP00000375844.2	Q9HC96-1
CAPN10	ENST00000354082.8	TSL:1	c.8C>A	p.Ala3Glu	missense	Exon 1 of 10	ENSP00000270362.6	Q9HC96-3
CAPN10	ENST00000352879.8	TSL:1	c.8C>A	p.Ala3Glu	missense	Exon 1 of 4	ENSP00000289381.6	Q9HC96-8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000157

AC:

AN:

1276540

Hom.:

Cov.:

AF XY:

0.00000319

AC XY:

AN XY:

626576

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

25558

American (AMR)

AF:

0.00

AC:

AN:

18828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21334

East Asian (EAS)

AF:

0.00

AC:

AN:

27628

South Asian (SAS)

AF:

0.00

AC:

AN:

65624

European-Finnish (FIN)

AF:

0.0000281

AC:

AN:

35560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4094

European-Non Finnish (NFE)

AF:

9.75e-7

AC:

AN:

1025292

Other (OTH)

AF:

0.00

AC:

AN:

52622

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Benign

-0.066

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.25

MetaSVM

Uncertain

0.36

MutationAssessor

Benign

1.9

PhyloP100

0.92

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.61

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.97

Vest4

0.49

MutPred

0.32

Loss of MoRF binding (P = 0.003)

MVP

0.93

MPC

0.87

ClinPred

0.87

GERP RS

2.5

PromoterAI

0.036

Neutral

(source)

Varity_R

0.31

gMVP

0.44

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over