16-547229-A-C

Position:

chr16-547229-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_005632.3(CAPN15):c.391A>C(p.Lys131Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000532 in 1,521,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

CAPN15
NM_005632.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.306

Variant links:

Genes affected

CAPN15 (HGNC:11182): (calpain 15) This gene encodes a protein containing zinc-finger-like repeats and a calpain-like protease domain. The encoded protein may function as a transcription factor, RNA-binding protein, or in protein-protein interactions during visual system development. [provided by RefSeq, Jul 2008]

CAPN15 links:

ENSG00000261691 (HGNC:):

ENSG00000261691 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0080989).

BP6

Variant 16-547229-A-C is Benign according to our data. Variant chr16-547229-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3263200.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000497 (68/1369470) while in subpopulation EAS AF= 0.000355 (13/36670). AF 95% confidence interval is 0.000209. There are 0 homozygotes in gnomad4_exome. There are 30 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN15	NM_005632.3 linkuse as main transcript	c.391A>C	p.Lys131Gln	missense_variant	4/14	ENST00000219611.7	NP_005623.1	O75808-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN15	ENST00000219611.7 linkuse as main transcript	c.391A>C	p.Lys131Gln	missense_variant	4/14	1	NM_005632.3	ENSP00000219611.2		O75808-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

125254

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

67152

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000175

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000396

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000497

AC:

AN:

1369470

Hom.:

Cov.:

AF XY:

0.0000445

AC XY:

AN XY:

674408

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000355

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000429

Gnomad4 OTH exome

AF:

0.0000350

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

ExAC

AF:

0.0000262

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.57

DANN

Benign

0.21

DEOGEN2

Benign

0.0096

T;T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.33

T;T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.0081

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.38

N;N;.

REVEL

Benign

0.21

Sift

Benign

0.58

T;T;.

Sift4G

Benign

0.57

T;T;.

Polyphen

0.0030

.;B;.

Vest4

0.11

MutPred

0.28

Loss of ubiquitination at K131 (P = 0.0087);Loss of ubiquitination at K131 (P = 0.0087);.;

MVP

0.41

ClinPred

0.0069

GERP RS

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.0

Varity_R

0.029

gMVP

0.18

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