Genetic Variant NM_001359.2:c.77G>C (chr8-90017131-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001359.2(DECR1):c.77G>C(p.Ser26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S26I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DECR1
NM_001359.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.49

Publications

0 publications found

Variant links:

Genes affected

DECR1 (HGNC:2753): (2,4-dienoyl-CoA reductase 1) Enables 2,4-dienoyl-CoA reductase (NADPH) activity; NADPH binding activity; and identical protein binding activity. Involved in fatty acid beta-oxidation. Located in cytosol; mitochondrion; and nucleoplasm. Part of catalytic complex. [provided by Alliance of Genome Resources, Apr 2022]

DECR1 Gene-Disease associations (from GenCC):

liver disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
progressive encephalopathy with leukodystrophy due to DECR deficiency
Inheritance: Unknown Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

DECR1 links:

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ACMG classification

Classification was made for transcript

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_001359.2. 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
	DECR1	NM_001359.2	MANE Select	c.77G>C	p.Ser26Thr	missense	Exon 2 of 10	NP_001350.1	Q16698-1
	DECR1	NM_001330575.2		c.50G>C	p.Ser17Thr	missense	Exon 4 of 12	NP_001317504.1	Q16698-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DECR1	ENST00000220764.7	TSL:1 MANE Select	c.77G>C	p.Ser26Thr	missense	Exon 2 of 10	ENSP00000220764.2	Q16698-1
DECR1	ENST00000519328.5	TSL:1	n.70-1778G>C		intron	N/A	ENSP00000431045.1	E5RGS6
DECR1	ENST00000886497.1		c.77G>C	p.Ser26Thr	missense	Exon 2 of 11	ENSP00000556556.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459402

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33350

American (AMR)

AF:

0.00

AC:

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

85798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110602

Other (OTH)

AF:

0.00

AC:

AN:

60294

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Uncertain

0.075

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

Eigen

Benign

0.057

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.56

M_CAP

Benign

0.032

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.4

PhyloP100

3.5

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.65

REVEL

Uncertain

0.33

Sift

Benign

0.11

Sift4G

Benign

0.31

Polyphen

0.0020

Vest4

0.19

MutPred

0.33

Gain of phosphorylation at S26 (P = 0.1133)

MVP

0.88

MPC

0.046

ClinPred

0.62

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.15

gMVP

0.75

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.44

Position offset: -7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over