chr6-44169433-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007058.4(CAPN11):​c.241G>A​(p.Glu81Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,230 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CAPN11
NM_007058.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.814
Variant links:
Genes affected
CAPN11 (HGNC:1478): (calpain 11) Calpains constitute a family of intracellular calcium-dependent cysteine proteases. There are eight members in this superfamily. They consist of a variable 80 kDa subunit and an invariant 30 kDa subunit. This calpain protein appears to have protease activity and calcium-binding ability. A similar mouse protein may play a functional role in spermatogenesis and in the regulation of calcium-dependent signal transduction events during meiosis. [provided by RefSeq, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.088611215).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAPN11NM_007058.4 linkc.241G>A p.Glu81Lys missense_variant Exon 3 of 23 ENST00000398776.2 NP_008989.2 Q9UMQ6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAPN11ENST00000398776.2 linkc.241G>A p.Glu81Lys missense_variant Exon 3 of 23 1 NM_007058.4 ENSP00000381758.1 Q9UMQ6
CAPN11ENST00000532171.5 linkc.331G>A p.Glu111Lys missense_variant Exon 4 of 6 4 ENSP00000432420.1 E9PQZ4
CAPN11ENST00000526118.1 linkn.*253G>A non_coding_transcript_exon_variant Exon 4 of 5 4 ENSP00000431963.1 E9PIX3
CAPN11ENST00000526118.1 linkn.*253G>A 3_prime_UTR_variant Exon 4 of 5 4 ENSP00000431963.1 E9PIX3

Frequencies

GnomAD3 genomes
AF:
0.000309
AC:
47
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000486
AC:
12
AN:
246948
AF XY:
0.0000596
show subpopulations
Gnomad AFR exome
AF:
0.000530
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000112
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000329
AC:
48
AN:
1460968
Hom.:
0
Cov.:
32
AF XY:
0.0000358
AC XY:
26
AN XY:
726708
show subpopulations
African (AFR)
AF:
0.000896
AC:
30
AN:
33470
American (AMR)
AF:
0.0000224
AC:
1
AN:
44612
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26072
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39692
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86062
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53366
Middle Eastern (MID)
AF:
0.000520
AC:
3
AN:
5766
European-Non Finnish (NFE)
AF:
0.00000990
AC:
11
AN:
1111582
Other (OTH)
AF:
0.0000331
AC:
2
AN:
60346
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000322
AC:
49
AN:
152262
Hom.:
0
Cov.:
32
AF XY:
0.000309
AC XY:
23
AN XY:
74450
show subpopulations
African (AFR)
AF:
0.00106
AC:
44
AN:
41544
American (AMR)
AF:
0.00
AC:
0
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000387
AC:
2
AN:
5174
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68026
Other (OTH)
AF:
0.00
AC:
0
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
3
6
9
12
15
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000113
Hom.:
0
Bravo
AF:
0.000295
ESP6500AA
AF:
0.000532
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000497
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 21, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.241G>A (p.E81K) alteration is located in exon 3 (coding exon 3) of the CAPN11 gene. This alteration results from a G to A substitution at nucleotide position 241, causing the glutamic acid (E) at amino acid position 81 to be replaced by a lysine (K). 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
0.087
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.085
.;T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.11
N
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.089
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;L
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.037
Sift
Benign
0.11
T;T
Sift4G
Benign
0.074
T;T
Polyphen
0.066
.;B
Vest4
0.18
MVP
0.39
MPC
0.14
ClinPred
0.026
T
GERP RS
1.3
Varity_R
0.12
gMVP
0.60
Mutation Taster
=90/10
polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201806418; hg19: chr6-44137170; COSMIC: COSV104706082; API