chr10-113729393-C-T

Position:

• chr10-113729393-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033340.4(CASP7):​c.731C>T​(p.Thr244Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CASP7 NM_033340.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741

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]

CASP7 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058081895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP7	NM_001227.5	c.765C>T	p.Asp255Asp	synonymous_variant	7/7	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.765C>T	p.Asp255Asp	synonymous_variant	7/7	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.9
DANN	Uncertain	0.99
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.43	.;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.83	N;.
REVEL	Benign	0.050
Sift	Uncertain	0.0030	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.053	B;B
Vest4		0.14
MutPred		0.44		Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);
MVP		0.30
ClinPred		0.084	T
GERP RS		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs2227310; hg19: chr10-115489152;