rs10901431

Variant names:

• chr10-125785806-T-C
• rs10901431
• ENST00000622016.4:c.274A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-125785806-T-C
• chr10-125785806-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000622016.4(UROS):​c.274A>G​(p.Met92Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,206 control chromosomes in the GnomAD database, including 16,580 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (16579 hom., cov: 33)
  • Exomes 𝑓: 0.42 (1 hom.)
• Consequence: UROS ENST00000622016.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 22 publications found

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: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.0616264E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000622016.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROS	NR_136677.2		n.950A>G		non_coding_transcript_exon	Exon 10 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROS	ENST00000622016.4	TSL:5	c.274A>G	p.Met92Val	missense	Exon 4 of 4	ENSP00000483041.1	A0A087X021
	UROS	ENST00000616800.4	TSL:5	c.160-546A>G		intron	N/A	ENSP00000482520.1	A0A087WZB7

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70265 AN: 152064 Hom.: 16553 Cov.: 33

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.417 AC: 10 AN: 24 Hom.: 1 Cov.: 0 AF XY: 0.438 AC XY: 7 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 8 AN: 16

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.462 AC: 70339 AN: 152182 Hom.: 16579 Cov.: 33 AF XY: 0.456 AC XY: 33951 AN XY: 74412

African (AFR) AF: 0.528 AC: 21918 AN: 41506

American (AMR) AF: 0.344 AC: 5260 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1368 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1665 AN: 5182

South Asian (SAS) AF: 0.455 AC: 2195 AN: 4826

European-Finnish (FIN) AF: 0.429 AC: 4540 AN: 10588

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31851 AN: 67996

Other (OTH) AF: 0.455 AC: 962 AN: 2116

Alfa AF: 0.462 Hom.: 40678

Bravo AF: 0.456

TwinsUK AF: 0.463 AC: 1716

ALSPAC AF: 0.477 AC: 1840

Asia WGS AF: 0.400 AC: 1393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.95	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.73
DEOGEN2	Benign	0.023	T
FATHMM_MKL	Benign	0.00058	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.00051	T
PhyloP100		-2.0
Sift4G	Benign	0.071	T
MVP		0.37
GERP RS		-0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10901431; hg19: chr10-127474375;