8-90020942-T-C

Variant names:

• chr8-90020942-T-C
• rs1272214940
• NM_001359.2:c.451T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001359.2(DECR1):​c.451T>C​(p.Ser151Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000028 in 1,431,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: DECR1 NM_001359.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802

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.451T>C	p.Ser151Pro	missense	Exon 5 of 10	NP_001350.1	Q16698-1
	DECR1	NM_001330575.2		c.424T>C	p.Ser142Pro	missense	Exon 7 of 12	NP_001317504.1	Q16698-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DECR1	ENST00000220764.7	TSL:1 MANE Select	c.451T>C	p.Ser151Pro	missense	Exon 5 of 10	ENSP00000220764.2	Q16698-1
	DECR1	ENST00000519328.5	TSL:1	n.*122T>C		non_coding_transcript_exon	Exon 4 of 8	ENSP00000431045.1	E5RGS6
	DECR1	ENST00000519328.5	TSL:1	n.*122T>C		3_prime_UTR	Exon 4 of 8	ENSP00000431045.1	E5RGS6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000891 AC: 2 AN: 224378 AF XY: 0.0000164

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000125

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000280 AC: 4 AN: 1431078 Hom.: 0 Cov.: 30 AF XY: 0.00000562 AC XY: 4 AN XY: 711172

African (AFR) AF: 0.00 AC: 0 AN: 31550

American (AMR) AF: 0.00 AC: 0 AN: 37452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25212

East Asian (EAS) AF: 0.000105 AC: 4 AN: 38056

South Asian (SAS) AF: 0.00 AC: 0 AN: 80336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100590

Other (OTH) AF: 0.00 AC: 0 AN: 59136

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.3	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.64
MutPred		0.51		Loss of stability (P = 0.073)
MVP		0.97
MPC		0.36
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.95
gMVP		0.94
Mutation Taster		=47/53	disease causing

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: rs1272214940; hg19: chr8-91033170;