3-9867263-C-T

Variant names:

• chr3-9867263-C-T
• rs1132704
• ENST00000443115.1:c.241G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The ENST00000443115.1(CIDEC):​c.241G>A​(p.Gly81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: CIDEC ENST00000443115.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.39
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.120973796).
• BP6: Variant 3-9867263-C-T is Benign according to our data. Variant chr3-9867263-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 738431.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	NM_001321142.2	MANE Select	c.588G>A	p.Gln196Gln	synonymous	Exon 7 of 7	NP_001308071.1	Q96AQ7-1
	CIDEC	NM_001199623.2		c.627G>A	p.Gln209Gln	synonymous	Exon 6 of 6	NP_001186552.1	A0A0A0MRY9
	CIDEC	NM_001199551.2		c.618G>A	p.Gln206Gln	synonymous	Exon 7 of 7	NP_001186480.1	Q96AQ7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIDEC	ENST00000443115.1	TSL:1	c.241G>A	p.Gly81Ser	missense	Exon 3 of 3	ENSP00000411356.1	A0A0C4DG75
	CIDEC	ENST00000336832.7	TSL:1 MANE Select	c.588G>A	p.Gln196Gln	synonymous	Exon 7 of 7	ENSP00000338642.2	Q96AQ7-1
	CIDEC	ENST00000383817.5	TSL:1	c.627G>A	p.Gln209Gln	synonymous	Exon 6 of 6	ENSP00000373328.2	A0A0A0MRY9

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152270 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000159 AC: 40 AN: 251274 AF XY: 0.000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000246 AC: 359 AN: 1461788 Hom.: 0 Cov.: 33 AF XY: 0.000259 AC XY: 188 AN XY: 727182

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44720

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

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53366

Middle Eastern (MID) AF: 0.000869 AC: 5 AN: 5756

European-Non Finnish (NFE) AF: 0.000274 AC: 305 AN: 1111982

Other (OTH) AF: 0.000232 AC: 14 AN: 60392

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152270 Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6 AN XY: 74396

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000168 Hom.: 0

Bravo AF: 0.000128

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000382

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	6.5
DANN	Benign	0.88
Eigen	Benign	-0.085
Eigen_PC	Benign	-0.088
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.090
Sift	Pathogenic	0.0	D
Vest4		0.18
MVP		0.56
ClinPred		0.11	T
GERP RS		3.5
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1132704; hg19: chr3-9908947;