Variant 6-44166826-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007058.4(CAPN11):c.85G>C(p.Ala29Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000786 in 1,398,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

CAPN11
NM_007058.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.625

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]

CAPN11 links:

POLR1C (HGNC:):

POLR1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066773176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN11	NM_007058.4 linkuse as main transcript	c.85G>C	p.Ala29Pro	missense_variant	2/23	ENST00000398776.2	NP_008989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CAPN11	ENST00000398776.2 linkuse as main transcript	c.85G>C	p.Ala29Pro	missense_variant	2/23	1	NM_007058.4	ENSP00000381758	P1
CAPN11	ENST00000532171.5 linkuse as main transcript	c.85G>C	p.Ala29Pro	missense_variant	2/6	4		ENSP00000432420
CAPN11	ENST00000526118.1 linkuse as main transcript	c.*97G>C		3_prime_UTR_variant, NMD_transcript_variant	3/5	4		ENSP00000431963

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000627

AC:

AN:

159602

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83934

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000161

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000786

AC:

AN:

1398728

Hom.:

Cov.:

AF XY:

0.00000725

AC XY:

AN XY:

689958

show subpopulations

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:

0.00000928

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.85G>C (p.A29P) alteration is located in exon 2 (coding exon 2) of the CAPN11 gene. This alteration results from a G to C substitution at nucleotide position 85, causing the alanine (A) at amino acid position 29 to be replaced by a proline (P). 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

0.071

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.46

DANN

Uncertain

0.98

DEOGEN2

Benign

0.00043

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.31

T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.29

Sift

Pathogenic

0.0

D;T

Sift4G

Pathogenic

0.0

D;T

Polyphen

0.84

.;P

Vest4

0.11

MutPred

0.21

Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);

MVP

0.38

MPC

0.11

ClinPred

0.10

GERP RS

-0.59

Varity_R

0.092

gMVP

0.20

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over