Genetic Variant NM_001321142.2:c.146C>A (chr3-9877127-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001321142.2(CIDEC):c.146C>A(p.Thr49Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. T49M) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CIDEC
NM_001321142.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

0 publications found

Variant links:

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

CIDEC links:

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ACMG classification

Classification was made for transcript

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=0.14812574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIDEC	NM_001321142.2 link	c.146C>A	p.Thr49Lys	missense_variant	Exon 4 of 7	ENST00000336832.7	NP_001308071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIDEC	ENST00000336832.7 link	c.146C>A	p.Thr49Lys	missense_variant	Exon 4 of 7	1	NM_001321142.2	ENSP00000338642.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1400256

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31686

American (AMR)

AF:

0.00

AC:

AN:

35770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25184

East Asian (EAS)

AF:

0.00

AC:

AN:

35972

South Asian (SAS)

AF:

0.00

AC:

AN:

79288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49352

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1079386

Other (OTH)

AF:

0.00

AC:

AN:

58050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.84

T;T;T;.;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.0

.;M;M;M;.

PhyloP100

1.2

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

.;.;N;N;N

REVEL

Benign

0.090

Sift

Uncertain

0.011

.;.;D;D;D

Sift4G

Uncertain

0.034

D;D;D;D;D

Polyphen

0.61

.;.;P;.;.

Vest4

0.13

MutPred

0.43

.;Loss of phosphorylation at T49 (P = 0.0061);Loss of phosphorylation at T49 (P = 0.0061);Loss of phosphorylation at T49 (P = 0.0061);Loss of phosphorylation at T49 (P = 0.0061);

MVP

0.49

MPC

0.022

ClinPred

0.73

GERP RS

-0.54

Varity_R

0.10

gMVP

0.53

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over