9-26892492-C-A

Variant names:

• chr9-26892492-C-A
• rs1823932294
• NM_024828.4:c.224G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024828.4(CAAP1):​c.224G>T​(p.Gly75Val) 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. 15/22 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: CAAP1 NM_024828.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• 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]

ENSG00000295750 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13774133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAAP1	NM_024828.4	c.224G>T	p.Gly75Val	missense_variant	Exon 1 of 6	ENST00000333916.8	NP_079104.3
CAAP1	XM_047423896.1	c.224G>T	p.Gly75Val	missense_variant	Exon 1 of 6		XP_047279852.1
CAAP1	NM_001167575.2	c.-366G>T		5_prime_UTR_variant	Exon 1 of 6		NP_001161047.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAAP1	ENST00000333916.8	c.224G>T	p.Gly75Val	missense_variant	Exon 1 of 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

Mar 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.224G>T (p.G75V) alteration is located in exon 1 (coding exon 1) of the CAAP1 gene. This alteration results from a G to T substitution at nucleotide position 224, causing the glycine (G) at amino acid position 75 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.0062	T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PhyloP100		2.6
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.70	N;D
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.094	T;D
Polyphen		0.0030	B;.
Vest4		0.36
MutPred		0.32		Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);
MVP		0.46
MPC		0.17
ClinPred		0.42	T
GERP RS		1.6
PromoterAI		-0.0080	Neutral
Varity_R		0.14
gMVP		0.30
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

dbSNP: rs1823932294; hg19: chr9-26892490;