Variant rs6753900 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_032977.4(CASP10):c.923-3C>A variant causes a splice region, splice polypyrimidine tract, intron change. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CASP10
NM_032977.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.9920

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

Variant links:

Genes affected

CASP10 (HGNC:1500): (caspase 10) This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene are associated with type IIA autoimmune lymphoproliferative syndrome, non-Hodgkin lymphoma and gastric cancer. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

CASP10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP10	NM_032977.4 linkuse as main transcript	c.923-3C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000286186.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP10	ENST00000286186.11 linkuse as main transcript	c.923-3C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032977.4	P2	Q92851-4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

136274

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000238

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000442

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000276

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000314

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000407

AC:

AN:

221166

Hom.:

AF XY:

0.0000498

AC XY:

AN XY:

120392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000107

Gnomad NFE exome

AF:

0.0000603

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00102

AC:

1248

AN:

1227302

Hom.:

Cov.:

AF XY:

0.000942

AC XY:

582

AN XY:

617578

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000311

Gnomad4 ASJ exome

AF:

0.000740

Gnomad4 EAS exome

AF:

0.000356

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.000792

Gnomad4 NFE exome

AF:

0.00118

Gnomad4 OTH exome

AF:

0.000856

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000733

AC:

AN:

136354

Hom.:

Cov.:

AF XY:

0.0000769

AC XY:

AN XY:

64998

show subpopulations

Gnomad4 AFR

AF:

0.0000265

Gnomad4 AMR

AF:

0.000237

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000443

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000276

Gnomad4 NFE

AF:

0.0000314

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000418

Hom.:

148

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

See cases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Dec 03, 2020

ACMG classification criteria: PM2, PM3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.76

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: 5

DS_AL_spliceai

0.29

Position offset: 3

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