3-9867275-G-C

Variant names:

• chr3-9867275-G-C
• rs1132703
• ENST00000443115.1:c.229C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000443115.1(CIDEC):​c.229C>G​(p.Leu77Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CIDEC ENST00000443115.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 0 publications found

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]

CIDEC Gene-Disease associations (from GenCC):

• CIDEC-related familial partial lipodystrophy

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000308530 (HGNC:):

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=0.14666903).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443115.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	NM_001321142.2	MANE Select	c.576C>G	p.Leu192Leu	synonymous	Exon 7 of 7	NP_001308071.1
	CIDEC	NM_001199623.2		c.615C>G	p.Leu205Leu	synonymous	Exon 6 of 6	NP_001186552.1
	CIDEC	NM_001199551.2		c.606C>G	p.Leu202Leu	synonymous	Exon 7 of 7	NP_001186480.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	ENST00000443115.1	TSL:1	c.229C>G	p.Leu77Val	missense	Exon 3 of 3	ENSP00000411356.1
	CIDEC	ENST00000336832.7	TSL:1 MANE Select	c.576C>G	p.Leu192Leu	synonymous	Exon 7 of 7	ENSP00000338642.2
	CIDEC	ENST00000383817.5	TSL:1	c.615C>G	p.Leu205Leu	synonymous	Exon 6 of 6	ENSP00000373328.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461806 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	7.5
DANN	Benign	0.84
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Vest4		0.15
MutPred		0.22		Loss of disorder (P = 0.1697)
MVP		0.38
ClinPred		0.87	D
GERP RS		1.4
Mutation Taster		=87/13	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

dbSNP: rs1132703; hg19: chr3-9908959;