10-113729393-C-T

Variant names:

• chr10-113729393-C-T
• rs2227310
• ENST00000369331.8:c.731C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 13/18 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. T244S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CASP7 NM_033340.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741
• Publications: 83 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: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033340.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	NM_001227.5	MANE Select	c.765C>T	p.Asp255Asp	synonymous	Exon 7 of 7	NP_001218.1	P55210-1
	CASP7	NM_033340.4		c.731C>T	p.Thr244Ile	missense	Exon 8 of 8	NP_203126.1	P55210-2
	CASP7	NM_001267057.1		c.1020C>T	p.Asp340Asp	synonymous	Exon 7 of 7	NP_001253986.1	P55210

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	ENST00000369331.8	TSL:1	c.731C>T	p.Thr244Ile	missense	Exon 8 of 8	ENSP00000358337.3	P55210-2
	CASP7	ENST00000369318.8	TSL:1 MANE Select	c.765C>T	p.Asp255Asp	synonymous	Exon 7 of 7	ENSP00000358324.4	P55210-1
	CASP7	ENST00000621607.4	TSL:1	c.864C>T	p.Asp288Asp	synonymous	Exon 7 of 7	ENSP00000478999.1	P55210-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3645

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
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
MetaSVM	Benign	-1.1	T
PhyloP100		-0.74
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.050
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.053	B
Vest4		0.14
MutPred		0.44		Loss of loop (P = 0.0022)
MVP		0.30
ClinPred		0.084	T
GERP RS		1.7
Mutation Taster		=95/5	polymorphism

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

dbSNP: rs2227310; hg19: chr10-115489152;