9-26887480-C-T

Position:

• chr9-26887480-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

CAAP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAAP1	NM_024828.4	c.337G>A	p.Glu113Lys	missense_variant	2/6	ENST00000333916.8	NP_079104.3
CAAP1	XM_047423896.1	c.337G>A	p.Glu113Lys	missense_variant	2/6		XP_047279852.1
CAAP1	NM_001167575.2	c.-99G>A		5_prime_UTR_variant	2/6		NP_001161047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAAP1	ENST00000333916.8	c.337G>A	p.Glu113Lys	missense_variant	2/6	1	NM_024828.4	ENSP00000369431.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.337G>A (p.E113K) alteration is located in exon 2 (coding exon 2) of the CAAP1 gene. This alteration results from a G to A substitution at nucleotide position 337, causing the glutamic acid (E) at amino acid position 113 to be replaced by a lysine (K). 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	0.21
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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

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