3-9870012-G-C

Variant names:

• chr3-9870012-G-C
• rs1414656804
• NM_001321142.2:c.424C>G

Variant summary

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

The NM_001321142.2(CIDEC):​c.424C>G​(p.Arg142Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R142C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CIDEC NM_001321142.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000308530 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321142.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	NM_001321142.2	MANE Select	c.424C>G	p.Arg142Gly	missense	Exon 6 of 7	NP_001308071.1	Q96AQ7-1
	CIDEC	NM_001199623.2		c.463C>G	p.Arg155Gly	missense	Exon 5 of 6	NP_001186552.1	A0A0A0MRY9
	CIDEC	NM_001199551.2		c.454C>G	p.Arg152Gly	missense	Exon 6 of 7	NP_001186480.1	Q96AQ7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	ENST00000336832.7	TSL:1 MANE Select	c.424C>G	p.Arg142Gly	missense	Exon 6 of 7	ENSP00000338642.2	Q96AQ7-1
	CIDEC	ENST00000383817.5	TSL:1	c.463C>G	p.Arg155Gly	missense	Exon 5 of 6	ENSP00000373328.2	A0A0A0MRY9
	CIDEC	ENST00000455015.6	TSL:1	c.202C>G	p.Arg68Gly	missense	Exon 5 of 6	ENSP00000392975.1	Q96AQ7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727244

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.064
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		1.6
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.31
Sift	Benign	0.035	D
Sift4G	Uncertain	0.037	D
Polyphen		0.0020	B
Vest4		0.44
MutPred		0.58		Loss of sheet (P = 0.0457)
MVP		0.86
MPC		0.038
ClinPred		0.78	D
GERP RS		1.7
Varity_R		0.24
gMVP		0.49
Mutation Taster		=85/15	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: rs1414656804; hg19: chr3-9911696;