9-26892477-T-C

Position:

• chr9-26892477-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024828.4(CAAP1):​c.239A>G​(p.Glu80Gly) 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. 12/21 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: CAAP1 NM_024828.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1257573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAAP1	NM_024828.4	c.239A>G	p.Glu80Gly	missense_variant	1/6	ENST00000333916.8	NP_079104.3
CAAP1	XM_047423896.1	c.239A>G	p.Glu80Gly	missense_variant	1/6		XP_047279852.1
CAAP1	NM_001167575.2	c.-351A>G		5_prime_UTR_variant	1/6		NP_001161047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAAP1	ENST00000333916.8	c.239A>G	p.Glu80Gly	missense_variant	1/6	1	NM_024828.4	ENSP00000369431.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Oct 06, 2022

The c.239A>G (p.E80G) alteration is located in exon 1 (coding exon 1) of the CAAP1 gene. This alteration results from a A to G substitution at nucleotide position 239, causing the glutamic acid (E) at amino acid position 80 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.75	N;D
REVEL	Benign	0.093
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.018	D;T
Polyphen		0.12	B;.
Vest4		0.30
MVP		0.14
MPC		0.16
ClinPred		0.36	T
GERP RS		1.9
Varity_R		0.12
gMVP		0.26

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: chr9-26892475;