3-9869889-T-A

Position:

• chr3-9869889-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321142.2(CIDEC):​c.547A>T​(p.Ile183Phe) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIDEC NM_001321142.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00200

Genes affected

CIDEC (HGNC:24229): (cell death inducing DFFA like effector c) This gene encodes a member of the cell death-inducing DNA fragmentation factor-like effector family. Members of this family play important roles in apoptosis. The encoded protein promotes lipid droplet formation in adipocytes and may mediate adipocyte apoptosis. This gene is regulated by insulin and its expression is positively correlated with insulin sensitivity. Mutations in this gene may contribute to insulin resistant diabetes. A pseudogene of this gene is located on the short arm of chromosome 3. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20500314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIDEC	NM_001321142.2	c.547A>T	p.Ile183Phe	missense_variant	6/7	ENST00000336832.7	NP_001308071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIDEC	ENST00000336832.7	c.547A>T	p.Ile183Phe	missense_variant	6/7	1	NM_001321142.2	ENSP00000338642	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.547A>T (p.I183F) alteration is located in exon 5 (coding exon 4) of the CIDEC gene. This alteration results from a A to T substitution at nucleotide position 547, causing the isoleucine (I) at amino acid position 183 to be replaced by a phenylalanine (F). 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	0.091
BayesDel_addAF	Benign	-0.0058	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	1.9
DANN	Benign	0.51
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.84	T;T;T;.;T;.
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.21	T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	.;.;L;.;.;.
MutationTaster	Benign	1.0	D;D;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	.;.;N;N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.092	.;.;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T;T
Polyphen		0.66	.;.;P;.;.;.
Vest4		0.28
MutPred		0.40		.;.;Loss of ubiquitination at K185 (P = 0.0919);.;.;.;
MVP		0.71
MPC		0.037
ClinPred		0.37	T
GERP RS		-4.1
Varity_R		0.11
gMVP		0.48

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: chr3-9911573;