Variant 16-546888-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005632.3(CAPN15):c.50C>T(p.Pro17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CAPN15
NM_005632.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32172948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPN15	NM_005632.3 linkuse as main transcript	c.50C>T	p.Pro17Leu	missense_variant	4/14	ENST00000219611.7	NP_005623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPN15	ENST00000219611.7 linkuse as main transcript	c.50C>T	p.Pro17Leu	missense_variant	4/14	1	NM_005632.3	ENSP00000219611	P1	O75808-1
CAPN15	ENST00000637507.1 linkuse as main transcript	c.254C>T	p.Pro85Leu	missense_variant	2/2	5		ENSP00000490480
CAPN15	ENST00000562370.5 linkuse as main transcript	c.50C>T	p.Pro17Leu	missense_variant	3/3	2		ENSP00000456017
CAPN15	ENST00000568988.5 linkuse as main transcript	c.-314-671C>T		intron_variant		3		ENSP00000457030

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

244140

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133572

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:

0.0000275

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1459168

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

725930

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:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000166

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 15, 2022

The c.50C>T (p.P17L) 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 50, causing the proline (P) at amino acid position 17 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;T;T

Eigen

Benign

0.041

Eigen_PC

Benign

0.066

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.86

D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.1

D;D;.

REVEL

Benign

0.12

Sift

Benign

0.21

T;D;.

Sift4G

Uncertain

0.0080

D;D;.

Polyphen

0.77

.;P;.

Vest4

0.35

MutPred

0.46

Loss of catalytic residue at P17 (P = 0.0246);Loss of catalytic residue at P17 (P = 0.0246);.;

MVP

0.24

ClinPred

0.61

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.096

gMVP

0.34

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