rs397514514

chr4-107947388-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_183075.3(CYP2U1):c.1139A>G(p.Glu380Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP2U1 NM_183075.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.56

Genes affected

CYP2U1 (HGNC:20582): (cytochrome P450 family 2 subfamily U member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This enzyme is a hydroxylase that metabolizes arachidonic acid, docosahexaenoic acid, and other long chain fatty acids. [provided by RefSeq, Jul 2008]

CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)

LOC107986298 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-107947388-A-G is Pathogenic according to our data. Variant chr4-107947388-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 39501.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.40172604).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2U1	NM_183075.3	c.1139A>G	p.Glu380Gly	missense_variant	3/5	ENST00000332884.11
LOC107986298	XR_001741784.2	n.204+31332T>C		intron_variant, non_coding_transcript_variant
CYP2U1	XM_005262717.2	c.1193A>G	p.Glu398Gly	missense_variant	3/5
CYP2U1	XM_005262720.2	c.503A>G	p.Glu168Gly	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2U1	ENST00000332884.11	c.1139A>G	p.Glu380Gly	missense_variant	3/5	1	NM_183075.3	P1
CYP2U1-AS1	ENST00000656249.1	n.80+31332T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary spastic paraplegia 56 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 07, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	0.64	D;D
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.43
Sift	Benign	0.031	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.010	B;.
Vest4		0.30
MutPred		0.51		Loss of disorder (P = 0.0844);.;
MVP		0.67
MPC		0.18
ClinPred		0.90	D
GERP RS		6.1
Varity_R		0.25
gMVP		0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs397514514; hg19: chr4-108868544;