chr10-113729492-C-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001227.5(CASP7):āc.864C>Gā(p.Ile288Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.0000075 ( 0 hom. )
Consequence
CASP7
NM_001227.5 missense
NM_001227.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: -0.779
Genes affected
CASP7 (HGNC:1508): (caspase 7) 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. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASP7 | NM_001227.5 | c.864C>G | p.Ile288Met | missense_variant | 7/7 | ENST00000369318.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASP7 | ENST00000369318.8 | c.864C>G | p.Ile288Met | missense_variant | 7/7 | 1 | NM_001227.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251436Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135892
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461868Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727238
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74352
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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 07, 2022 | The c.963C>G (p.I321M) alteration is located in exon 8 (coding exon 7) of the CASP7 gene. This alteration results from a C to G substitution at nucleotide position 963, causing the isoleucine (I) at amino acid position 321 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;.;D;.;.;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L;L;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;N;.;N;N;.;D
REVEL
Uncertain
Sift
Benign
.;T;.;T;T;.;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
D;D;.;D;D;D;.
Vest4
MutPred
Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);.;Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);.;.;
MVP
MPC
0.29
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at