16-57431254-A-G

Variant names:

• chr16-57431254-A-G
• NM_020313.4:c.643T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_020313.4(CIAPIN1):​c.643T>C​(p.Ser215Pro) 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)
• Consequence: CIAPIN1 NM_020313.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50

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.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity CPIN1_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIAPIN1	NM_020313.4	c.643T>C	p.Ser215Pro	missense_variant	Exon 7 of 9	ENST00000394391.9	NP_064709.2
CIAPIN1	NM_001308347.2	c.604T>C	p.Ser202Pro	missense_variant	Exon 7 of 9		NP_001295276.1
CIAPIN1	NM_001308358.2	c.631-915T>C		intron_variant	Intron 6 of 7		NP_001295287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIAPIN1	ENST00000394391.9	c.643T>C	p.Ser215Pro	missense_variant	Exon 7 of 9	1	NM_020313.4	ENSP00000377914.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.643T>C (p.S215P) alteration is located in exon 7 (coding exon 6) of the CIAPIN1 gene. This alteration results from a T to C substitution at nucleotide position 643, causing the serine (S) at amino acid position 215 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	Benign	0.19
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;D;T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.19	T;T;T;.
Polyphen		1.0	D;D;.;.
Vest4		0.34
MutPred		0.45		Loss of phosphorylation at S215 (P = 0.0082);.;.;.;
MVP		0.61
MPC		0.29
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.53

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: chr16-57465166;