rs10510149

chr10-125807238-A-Cchr10-125807238-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000375.3(UROS):c.394+175T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 644,030 control chromosomes in the GnomAD database, including 61,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (13837 hom., cov: 32)
  • Exomes 𝑓: 0.43 (47523 hom.)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.956

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 10-125807238-A-C is Benign according to our data. Variant chr10-125807238-A-C is described in ClinVar as [Benign]. Clinvar id is 1273846.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UROS	NM_000375.3	c.394+175T>G		intron_variant		ENST00000368797.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UROS	ENST00000368797.10	c.394+175T>G		intron_variant		1	NM_000375.3	P1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64184 AN: 151944 Hom.: 13821 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.434 AC: 213704 AN: 491968 Hom.: 47523 Cov.: 5 AF XY: 0.436 AC XY: 114485 AN XY: 262772

Gnomad4 AFR exome AF: 0.395

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.430

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.422 AC: 64231 AN: 152062 Hom.: 13837 Cov.: 32 AF XY: 0.417 AC XY: 31017 AN XY: 74334

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.425

Alfa AF: 0.445 Hom.: 20754

Bravo AF: 0.412

Asia WGS AF: 0.373 AC: 1298 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.43
Dann	Benign	0.41

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

LitVar

Other links and lift over

dbSNP: rs10510149; hg19: chr10-127495807;