10-125785806-T-G

Position:

• chr10-125785806-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000622016.4(UROS):​c.274A>C​(p.Met92Leu) 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. 6/7 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: not found (cov: 33)
• Consequence: UROS ENST00000622016.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07313642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UROS	XM_017016612.3	c.694A>C	p.Met232Leu	missense_variant	10/10		XP_016872101.1
UROS	XM_011540127.3	c.661-546A>C		intron_variant			XP_011538429.1
UROS	NR_136677.2	n.950A>C		non_coding_transcript_exon_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UROS	ENST00000622016.4	c.274A>C	p.Met92Leu	missense_variant	4/4	5		ENSP00000483041
UROS	ENST00000616800.4	c.161-546A>C		intron_variant		5		ENSP00000482520

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.76
DEOGEN2	Benign	0.0019	T
FATHMM_MKL	Benign	0.00068	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.073	T
Sift4G	Benign	0.37	T
MVP		0.38
GERP RS		-0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10901431; hg19: chr10-127474375;