9-26887480-C-T

Variant names:

• chr9-26887480-C-T
• rs1401125154
• NM_024828.4:c.337G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024828.4(CAAP1):​c.337G>A​(p.Glu113Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAAP1 NM_024828.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024828.4. 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
	CAAP1	NM_024828.4	MANE Select	c.337G>A	p.Glu113Lys	missense	Exon 2 of 6	NP_079104.3
	CAAP1	NM_001167575.2		c.-99G>A		5_prime_UTR	Exon 2 of 6	NP_001161047.1	Q9H8G2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAAP1	ENST00000333916.8	TSL:1 MANE Select	c.337G>A	p.Glu113Lys	missense	Exon 2 of 6	ENSP00000369431.3	Q9H8G2-1
	CAAP1	ENST00000903808.1		c.337G>A	p.Glu113Lys	missense	Exon 2 of 6	ENSP00000573867.1
	CAAP1	ENST00000924906.1		c.337G>A	p.Glu113Lys	missense	Exon 2 of 6	ENSP00000594965.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	0.21
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.63	N
PhyloP100		2.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.12
Sift	Benign	0.047	D
Sift4G	Benign	0.14	T
Polyphen		0.99	D
Vest4		0.34
MutPred		0.34		Gain of ubiquitination at E113 (P = 0.009)
MVP		0.19
MPC		0.36
ClinPred		0.78	D
GERP RS		5.6
Varity_R		0.15
gMVP		0.27
Mutation Taster		=289/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.39		Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1401125154; hg19: chr9-26887478; COSMIC: COSV100445211; COSMIC: COSV100445211;