9-26886166-T-C

Variant names:

• chr9-26886166-T-C
• NM_024828.4:c.527A>G

Variant summary

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

The NM_024828.4(CAAP1):​c.527A>G​(p.Lys176Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CAAP1 NM_024828.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.30
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAAP1	NM_024828.4	c.527A>G	p.Lys176Arg	missense_variant	Exon 3 of 6	ENST00000333916.8	NP_079104.3
CAAP1	NM_001167575.2	c.92A>G	p.Lys31Arg	missense_variant	Exon 3 of 6		NP_001161047.1
CAAP1	XM_047423896.1	c.527A>G	p.Lys176Arg	missense_variant	Exon 3 of 6		XP_047279852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAAP1	ENST00000333916.8	c.527A>G	p.Lys176Arg	missense_variant	Exon 3 of 6	1	NM_024828.4	ENSP00000369431.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1405282 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 697560

African (AFR) AF: 0.00 AC: 0 AN: 30748

American (AMR) AF: 0.00 AC: 0 AN: 35750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24656

East Asian (EAS) AF: 0.00 AC: 0 AN: 37944

South Asian (SAS) AF: 0.00 AC: 0 AN: 73190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4798

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088100

Other (OTH) AF: 0.00 AC: 0 AN: 57764

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.527A>G (p.K176R) alteration is located in exon 3 (coding exon 3) of the CAAP1 gene. This alteration results from a A to G substitution at nucleotide position 527, causing the lysine (K) at amino acid position 176 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.4	L;.
PhyloP100		6.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N;.
REVEL	Benign	0.25
Sift	Uncertain	0.027	D;.
Sift4G	Benign	0.074	T;T
Polyphen		1.0	D;.
Vest4		0.72
MutPred		0.45		Loss of methylation at K176 (P = 0.0069);.;
MVP		0.25
MPC		0.46
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.26
gMVP		0.24
Mutation Taster		=64/36	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

hg19: chr9-26886164;