NM_001227.5:c.151A>G

Variant names:

• chr10-113721072-A-G
• NM_001227.5:c.151A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001227.5(CASP7):​c.151A>G​(p.Thr51Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CASP7 NM_001227.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.01
• 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: 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=0.05028978).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001227.5. 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.151A>G	p.Thr51Ala	missense	Exon 3 of 7	NP_001218.1	P55210-1
	CASP7	NM_001267057.1		c.406A>G	p.Thr136Ala	missense	Exon 3 of 7	NP_001253986.1	P55210
	CASP7	NM_033338.6		c.250A>G	p.Thr84Ala	missense	Exon 4 of 8	NP_203124.1	P55210-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	ENST00000369318.8	TSL:1 MANE Select	c.151A>G	p.Thr51Ala	missense	Exon 3 of 7	ENSP00000358324.4	P55210-1
	CASP7	ENST00000621607.4	TSL:1	c.250A>G	p.Thr84Ala	missense	Exon 3 of 7	ENSP00000478999.1	P55210-3
	CASP7	ENST00000345633.8	TSL:1	c.151A>G	p.Thr51Ala	missense	Exon 4 of 8	ENSP00000298701.7	P55210-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.019
DANN	Benign	0.52
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-2.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.029
Sift	Benign	0.73	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.085
MutPred		0.32		Loss of phosphorylation at T51 (P = 0.015)
MVP		0.21
MPC		0.15
ClinPred		0.040	T
GERP RS		-12
Varity_R		0.054
gMVP		0.29
Mutation Taster		=93/7	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

hg19: chr10-115480831;