dbSNP rs7607759: CAPN10:p.Thr504Pro (chr2-240596709-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_023083.4(CAPN10):c.1510A>C(p.Thr504Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,411,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. T504A) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CAPN10
NM_023083.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

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 Gene-Disease associations (from GenCC):

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

CAPN10 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=0.107094586).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN10	NM_023083.4	MANE Select	c.1510A>C	p.Thr504Pro	missense	Exon 9 of 12	NP_075571.2
	CAPN10	NM_023085.4		c.1279-1179A>C		intron	N/A	NP_075573.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CAPN10	ENST00000391984.7	TSL:1 MANE Select	c.1510A>C	p.Thr504Pro	missense	Exon 9 of 12	ENSP00000375844.2
CAPN10	ENST00000270361.15	TSL:1	n.*674A>C		non_coding_transcript_exon	Exon 9 of 12	ENSP00000270361.11
CAPN10	ENST00000270361.15	TSL:1	n.*674A>C		3_prime_UTR	Exon 9 of 12	ENSP00000270361.11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.09e-7

AC:

AN:

1411400

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

696312

show subpopulations

African (AFR)

AF:

0.0000310

AC:

AN:

32282

American (AMR)

AF:

0.00

AC:

AN:

39624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22562

East Asian (EAS)

AF:

0.00

AC:

AN:

39262

South Asian (SAS)

AF:

0.00

AC:

AN:

77986

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085980

Other (OTH)

AF:

0.00

AC:

AN:

58154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.093

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.071

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.32

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.90

PhyloP100

-1.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.32

REVEL

Benign

0.24

Sift

Benign

0.11

Sift4G

Benign

0.28

Polyphen

0.0

Vest4

0.13

MutPred

0.45

Gain of relative solvent accessibility (P = 0.0289)

MVP

0.57

MPC

0.48

ClinPred

0.032

GERP RS

-3.0

Varity_R

0.078

gMVP

0.44

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over