Variant 16-546992-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005632.3(CAPN15):c.154C>T(p.Arg52Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,457,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CAPN15
NM_005632.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN15	NM_005632.3 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	4/14	ENST00000219611.7	NP_005623.1	O75808-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAPN15	ENST00000219611.7 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	4/14	1	NM_005632.3	ENSP00000219611.2	O75808-1
CAPN15	ENST00000637507.1 linkuse as main transcript	c.358C>T	p.Arg120Cys	missense_variant	2/2	5		ENSP00000490480.1	A0A1B0GVE3
CAPN15	ENST00000562370.5 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	3/3	2		ENSP00000456017.1	H3BR03
CAPN15	ENST00000568988.5 linkuse as main transcript	c.-314-567C>T		intron_variant		3		ENSP00000457030.1	H3BT55

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245404

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

133986

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1457832

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725422

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000339

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

AC:

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

Dec 27, 2022

The c.154C>T (p.R52C) alteration is located in exon 4 (coding exon 1) of the CAPN15 gene. This alteration results from a C to T substitution at nucleotide position 154, causing the arginine (R) at amino acid position 52 to be replaced by a cysteine (C). 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

0.31

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;T;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.1

.;M;.

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-4.6

D;D;.

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

.;D;.

Vest4

0.83

MutPred

0.52

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;

MVP

0.17

ClinPred

0.98

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.64

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