10-125795395-T-C

Position:

• chr10-125795395-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000375.3(UROS):​c.562-417A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,148 control chromosomes in the GnomAD database, including 15,990 homozygotes. 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: 𝑓 0.45 (15990 hom., cov: 33)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UROS	NM_000375.3	c.562-417A>G		intron_variant		ENST00000368797.10	NP_000366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UROS	ENST00000368797.10	c.562-417A>G		intron_variant		1	NM_000375.3	ENSP00000357787	P1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69121 AN: 152030 Hom.: 15975 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.455 AC: 69173 AN: 152148 Hom.: 15990 Cov.: 33 AF XY: 0.449 AC XY: 33372 AN XY: 74372

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.452

Alfa AF: 0.452 Hom.: 2632

Bravo AF: 0.447

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.7
DANN	Benign	0.66

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: rs10751533; hg19: chr10-127483964; COSMIC: COSV64230056; COSMIC: COSV64230056;