rs1804886

chr1-45014762-T-A

Variant summary

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

The NM_000374.5(UROD):c.801T>A(p.Phe267Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UROD NM_000374.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

Genes affected

UROD (HGNC:12591): (uroporphyrinogen decarboxylase) This gene encodes an enzyme in the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains. Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoetic porphyria.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27832687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UROD	NM_000374.5	c.801T>A	p.Phe267Leu	missense_variant	8/10	ENST00000246337.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UROD	ENST00000246337.9	c.801T>A	p.Phe267Leu	missense_variant	8/10	1	NM_000374.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D;T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.087
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.68	N;.;.
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.2	D;.;.
REVEL	Uncertain	0.34
Sift	Benign	0.034	D;.;.
Sift4G	Benign	0.26	T;.;.
Polyphen		0.099	B;.;.
Vest4		0.55
MutPred		0.38		Loss of catalytic residue at F267 (P = 0.0323);.;Loss of catalytic residue at F267 (P = 0.0323);
MVP		0.92
MPC		0.76
ClinPred		0.92	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1804886; hg19: chr1-45480434;