Genetic Variant UROS:c.-26-177T>A (chr10-125816702-A-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_000375.3(UROS):c.-26-177T>A variant causes a intron change. The variant allele was found at a frequency of 0.00000202 in 494,254 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Consequence

UROS
NM_000375.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.75

Publications

0 publications found

Variant links:

Genes affected

UROS (HGNC:12592): (uroporphyrinogen III synthase) The protein encoded by this gene catalyzes the fourth step of porphyrin biosynthesis in the heme biosynthetic pathway. Defects in this gene cause congenital erythropoietic porphyria (Gunther's disease). [provided by RefSeq, Jul 2008]

UROS Gene-Disease associations (from GenCC):

cutaneous porphyria
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet

UROS 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 (BayesDel_noAF=-0.22).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UROS	NM_000375.3 link	c.-26-177T>A		intron_variant	Intron 1 of 9	ENST00000368797.10	NP_000366.1	P10746A0A0S2Z4T8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UROS	ENST00000368797.10 link	c.-26-177T>A		intron_variant	Intron 1 of 9	1	NM_000375.3	ENSP00000357787.4		P10746

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000202

AC:

AN:

494254

Hom.:

AF XY:

0.00

AC XY:

AN XY:

262588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13654

American (AMR)

AF:

0.00

AC:

AN:

25594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15382

East Asian (EAS)

AF:

0.00

AC:

AN:

31488

South Asian (SAS)

AF:

0.00

AC:

AN:

49960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2230

European-Non Finnish (NFE)

AF:

0.00000336

AC:

AN:

297522

Other (OTH)

AF:

0.00

AC:

AN:

27820

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

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

4.7

PromoterAI

-0.16

Neutral

(source)

Mutation Taster

=3/97

disease causing

(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