Variant 11-104890403-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000375726.6(CASP12):c.788A>T(p.Asp263Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,382,248 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CASP12
ENST00000375726.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18

Variant links:

Genes affected

CASP12 (HGNC:19004): (caspase 12 (gene/pseudogene)) Caspases are cysteine proteases that cleave C-terminal aspartic acid residues on their substrate molecules. This gene is most highly related to members of the ICE subfamily of caspases that process inflammatory cytokines. In rodents, the homolog of this gene mediates apoptosis in response to endoplasmic reticulum stress. However, in humans this gene contains a polymorphism for the presence or absence of a premature stop codon. The majority of human individuals have the premature stop codon and produce a truncated non-functional protein. The read-through codon occurs primarily in individuals of African descent and carriers have endotoxin hypo-responsiveness and an increased susceptibility to severe sepsis. Several alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Feb 2011]

CASP12 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	UniProt
CASP12	NR_034068.4 linkuse as main transcript	n.347A>T		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP12	ENST00000613512.4 linkuse as main transcript	c.788A>T	p.Asp263Val	missense_variant	5/8	1		P5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000717

AC:

AN:

139414

Hom.:

AF XY:

0.00

AC XY:

AN XY:

75402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000409

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.23e-7

AC:

AN:

1382248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 08, 2023

The c.788A>T (p.D263V) alteration is located in exon 5 (coding exon 5) of the CASP12 gene. This alteration results from a A to T substitution at nucleotide position 788, causing the aspartic acid (D) at amino acid position 263 to be replaced by a valine (V). 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

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.41

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Benign

0.19

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.065

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.74

MutationTaster

Benign

1.0

D;D;D;D;N;N;N;N;N

PrimateAI

Uncertain

0.52

REVEL

Uncertain

0.50

Vest4

0.79

MVP

0.25

MPC

0.16

ClinPred

0.99

GERP RS

2.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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