chr9-26884873-A-G

Variant names:

• chr9-26884873-A-G
• rs570695283
• NM_024828.4:c.602T>C

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.602T>C​(p.Met201Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M201R) has been classified 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: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAAP1	NM_024828.4	c.602T>C	p.Met201Thr	missense_variant	Exon 4 of 6	ENST00000333916.8	NP_079104.3
CAAP1	NM_001167575.2	c.167T>C	p.Met56Thr	missense_variant	Exon 4 of 6		NP_001161047.1
CAAP1	XM_047423896.1	c.602T>C	p.Met201Thr	missense_variant	Exon 4 of 6		XP_047279852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAAP1	ENST00000333916.8	c.602T>C	p.Met201Thr	missense_variant	Exon 4 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: 1454832 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724178

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 86006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109360

Other (OTH) AF: 0.00 AC: 0 AN: 60242

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.81
DEOGEN2	Benign	0.0024	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.14	N;.
REVEL	Benign	0.038
Sift	Benign	0.38	T;.
Sift4G	Benign	0.37	T;T
Polyphen		0.0	B;.
Vest4		0.20
MutPred		0.27		Loss of stability (P = 0.0044);.;
MVP		0.18
MPC		0.15
ClinPred		0.28	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.083
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs570695283; hg19: chr9-26884871;