16-57430328-A-G

Variant names:

• chr16-57430328-A-G
• rs1903059280
• NM_020313.4:c.758T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020313.4(CIAPIN1):​c.758T>C​(p.Leu253Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIAPIN1 NM_020313.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

Genes affected

CIAPIN1 (HGNC:28050): (cytokine induced apoptosis inhibitor 1) CIAPIN1 is a cytokine-induced inhibitor of apoptosis with no relation to apoptosis regulatory molecules of the BCL2 (MIM 151430) or CASP (see MIM 147678) families. Expression of CIAPIN1 is dependent on growth factor stimulation (Shibayama et al., 2004 [PubMed 14970183]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIAPIN1	NM_020313.4	c.758T>C	p.Leu253Pro	missense_variant	Exon 8 of 9	ENST00000394391.9	NP_064709.2
CIAPIN1	NM_001308347.2	c.719T>C	p.Leu240Pro	missense_variant	Exon 8 of 9		NP_001295276.1
CIAPIN1	NM_001308358.2	c.642T>C	p.Pro214Pro	synonymous_variant	Exon 7 of 8		NP_001295287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIAPIN1	ENST00000394391.9	c.758T>C	p.Leu253Pro	missense_variant	Exon 8 of 9	1	NM_020313.4	ENSP00000377914.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.758T>C (p.L253P) alteration is located in exon 8 (coding exon 7) of the CIAPIN1 gene. This alteration results from a T to C substitution at nucleotide position 758, causing the leucine (L) at amino acid position 253 to be replaced by a proline (P). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.73	D;.;T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.9	H;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.4	D;D;D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.93
MutPred		0.71		Loss of catalytic residue at L253 (P = 0.0135);.;.;
MVP		0.72
MPC		1.0
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.94
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs1903059280; hg19: chr16-57464240;