9-26884832-T-A

Variant names:

• chr9-26884832-T-A
• NM_024828.4:c.643A>T

Variant summary

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

The NM_024828.4(CAAP1):​c.643A>T​(p.Met215Leu) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAAP1 NM_024828.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

Genes affected

CAAP1 (HGNC:25834): (caspase activity and apoptosis inhibitor 1) Involved in negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

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=0.043589354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAAP1	NM_024828.4	c.643A>T	p.Met215Leu	missense_variant	Exon 4 of 6	ENST00000333916.8	NP_079104.3
CAAP1	NM_001167575.2	c.208A>T	p.Met70Leu	missense_variant	Exon 4 of 6		NP_001161047.1
CAAP1	XM_047423896.1	c.643A>T	p.Met215Leu	missense_variant	Exon 4 of 6		XP_047279852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAAP1	ENST00000333916.8	c.643A>T	p.Met215Leu	missense_variant	Exon 4 of 6	1	NM_024828.4	ENSP00000369431.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.643A>T (p.M215L) alteration is located in exon 4 (coding exon 4) of the CAAP1 gene. This alteration results from a A to T substitution at nucleotide position 643, causing the methionine (M) at amino acid position 215 to be replaced by a leucine (L). 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	Benign	0.088
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.81
DEOGEN2	Benign	0.0037	T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.044	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.48	N;.
REVEL	Benign	0.045
Sift	Benign	0.72	T;.
Sift4G	Benign	0.46	T;T
Polyphen		0.0	B;.
Vest4		0.22
MutPred		0.13		Loss of phosphorylation at S217 (P = 0.2463);.;
MVP		0.17
MPC		0.12
ClinPred		0.53	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.048

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-26884830;