rs397515351

Variant names:

• chr10-125816722-G-C
• rs397515351
• NM_000375.3:c.-26-197C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-125816722-G-C
• chr10-125816722-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000375.3(UROS):​c.-26-197C>G variant causes a intron change. The variant allele was found at a frequency of 0.00000219 in 456,298 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: 0.0000022 (0 hom.)
• Consequence: UROS NM_000375.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.09
• Publications: 0 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UROS	NM_000375.3	c.-26-197C>G		intron_variant	Intron 1 of 9	ENST00000368797.10	NP_000366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UROS	ENST00000368797.10	c.-26-197C>G		intron_variant	Intron 1 of 9	1	NM_000375.3	ENSP00000357787.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000219 AC: 1 AN: 456298 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 241276

African (AFR) AF: 0.00 AC: 0 AN: 12638

American (AMR) AF: 0.00 AC: 0 AN: 20348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13982

East Asian (EAS) AF: 0.00 AC: 0 AN: 30962

South Asian (SAS) AF: 0.0000220 AC: 1 AN: 45548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2028

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 275266

Other (OTH) AF: 0.00 AC: 0 AN: 26230

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.74
PhyloP100		5.1
PromoterAI		-0.17	Neutral

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

Other links and lift over

dbSNP: rs397515351; hg19: chr10-127505291;