chr10-113725487-G-A

Variant names:

• chr10-113725487-G-A
• NM_001227.5:c.502G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_Strong BS2

The NM_001227.5(CASP7):​c.502G>A​(p.Gly168Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,450,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: CASP7 NM_001227.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.82
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.502G>A	p.Gly168Arg	missense_variant	Exon 5 of 7	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.502G>A	p.Gly168Arg	missense_variant	Exon 5 of 7	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000827 AC: 12 AN: 1450846 Hom.: 0 Cov.: 30 AF XY: 0.00000832 AC XY: 6 AN XY: 721480

African (AFR) AF: 0.00 AC: 0 AN: 32604

American (AMR) AF: 0.00 AC: 0 AN: 41352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25574

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 AN: 84418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1108528

Other (OTH) AF: 0.00 AC: 0 AN: 59822

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.601G>A (p.G201R) alteration is located in exon 6 (coding exon 5) of the CASP7 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the glycine (G) at amino acid position 201 to be replaced by an arginine (R). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T;T;T;T;T;T;.;.
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D;D;.;D;.;.;D;D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Pathogenic	3.9	H;.;H;.;H;H;.;.
PhyloP100		9.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.9	.;D;D;.;D;D;.;D
REVEL	Pathogenic	0.82
Sift	Pathogenic	0.0	.;D;D;.;D;D;.;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D;D
Polyphen		1.0	D;.;D;.;D;D;D;.
Vest4		0.79
MutPred		0.86		Gain of MoRF binding (P = 0.038);Gain of MoRF binding (P = 0.038);Gain of MoRF binding (P = 0.038);.;Gain of MoRF binding (P = 0.038);Gain of MoRF binding (P = 0.038);.;.;
MVP		0.91
MPC		0.73
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.95
gMVP		0.85
Mutation Taster		=9/91	disease causing

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

Other links and lift over

hg19: chr10-115485246;