rs573042092

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004347.5(CASP5):c.1082G>T(p.Cys361Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C361S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CASP5
NM_004347.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0240

Publications

0 publications found

Variant links:

Genes affected

CASP5 (HGNC:1506): (caspase 5) This gene encodes 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. Overexpression of the active form of this enzyme induces apoptosis in fibroblasts. Max, a central component of the Myc/Max/Mad transcription regulation network important for cell growth, differentiation, and apoptosis, is cleaved by this protein; this process requires Fas-mediated dephosphorylation of Max. The expression of this gene is regulated by interferon-gamma and lipopolysaccharide. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]

CASP5 links:

ENSG00000303891 (HGNC:):

ENSG00000303891 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3123356).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004347.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CASP5	NM_004347.5	MANE Select	c.1082G>T	p.Cys361Phe	missense	Exon 7 of 10	NP_004338.3	P51878-1
CASP5	NM_001136112.3		c.1121G>T	p.Cys374Phe	missense	Exon 7 of 10	NP_001129584.1	P51878-5
CASP5	NM_001136109.3		c.908G>T	p.Cys303Phe	missense	Exon 6 of 9	NP_001129581.1	P51878-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CASP5	ENST00000260315.8	TSL:5 MANE Select	c.1082G>T	p.Cys361Phe	missense	Exon 7 of 10	ENSP00000260315.3	P51878-1
CASP5	ENST00000393141.6	TSL:5	c.1121G>T	p.Cys374Phe	missense	Exon 7 of 10	ENSP00000376849.2	P51878-5
CASP5	ENST00000526056.5	TSL:5	c.1121G>T	p.Cys374Phe	missense	Exon 7 of 9	ENSP00000436877.1	P51878-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726906

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.00

AC:

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111728

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.066

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.69

M_CAP

Benign

0.015

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

-0.024

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.13

Sift

Benign

0.59

Sift4G

Benign

0.64

Polyphen

0.74

Vest4

0.20

MutPred

0.64

Gain of glycosylation at S363 (P = 0.0655)

MVP

0.46

MPC

0.50

ClinPred

0.83

GERP RS

1.3

Varity_R

0.29

gMVP

0.39

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over