dbSNP rs3749166: CAPN10:p.Ala620Ala (chr2-240598004-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_023083.4(CAPN10):c.1860G>A(p.Ala620Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,612,786 control chromosomes in the GnomAD database, including 287,257 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 0.52 ( 22198 hom., cov: 33)

Exomes 𝑓: 0.60 ( 265059 hom. )

Consequence

CAPN10
NM_023083.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

Publications

26 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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

CAPN10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN10	NM_023083.4 link	c.1860G>A	p.Ala620Ala	synonymous_variant	Exon 10 of 12	ENST00000391984.7	NP_075571.2	Q9HC96-1
CAPN10	NM_023085.4 link	c.1395G>A	p.Ala465Ala	synonymous_variant	Exon 8 of 10		NP_075573.3	Q9HC96-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN10	ENST00000391984.7 link	c.1860G>A	p.Ala620Ala	synonymous_variant	Exon 10 of 12	1	NM_023083.4	ENSP00000375844.2		Q9HC96-1

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79636

AN:

151872

Hom.:

22182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.721

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.657

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.554

GnomAD2 exomes

AF:

0.583

AC:

145961

AN:

250162

AF XY:

0.589

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.606

Gnomad ASJ exome

AF:

0.600

Gnomad EAS exome

AF:

0.659

Gnomad FIN exome

AF:

0.542

Gnomad NFE exome

AF:

0.613

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.600

AC:

875966

AN:

1460796

Hom.:

265059

Cov.:

AF XY:

0.600

AC XY:

436128

AN XY:

726736

show subpopulations

African (AFR)

AF:

0.300

AC:

10050

AN:

33480

American (AMR)

AF:

0.604

AC:

27011

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

15580

AN:

26126

East Asian (EAS)

AF:

0.645

AC:

25586

AN:

39698

South Asian (SAS)

AF:

0.573

AC:

49388

AN:

86246

European-Finnish (FIN)

AF:

0.552

AC:

29010

AN:

52598

Middle Eastern (MID)

AF:

0.517

AC:

2981

AN:

5766

European-Non Finnish (NFE)

AF:

0.612

AC:

680538

AN:

1111788

Other (OTH)

AF:

0.593

AC:

35822

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19451

38901

58352

77802

97253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18280

36560

54840

73120

91400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.524

AC:

79684

AN:

151990

Hom.:

22198

Cov.:

AF XY:

0.524

AC XY:

38953

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.320

AC:

13277

AN:

41458

American (AMR)

AF:

0.577

AC:

8826

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2103

AN:

3470

East Asian (EAS)

AF:

0.658

AC:

3388

AN:

5150

South Asian (SAS)

AF:

0.566

AC:

2727

AN:

4818

European-Finnish (FIN)

AF:

0.551

AC:

5824

AN:

10572

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.612

AC:

41543

AN:

67920

Other (OTH)

AF:

0.556

AC:

1175

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1869

3738

5607

7476

9345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.578

Hom.:

21281

Bravo

AF:

0.518

Asia WGS

AF:

0.594

AC:

2062

AN:

3478

EpiCase

AF:

0.602

EpiControl

AF:

0.601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.6

(source)

DANN

Benign

0.58

PhyloP100

-2.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.44

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over