rs10510149

Variant names:

• chr10-125807238-A-C
• rs10510149
• NM_000375.3:c.394+175T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-125807238-A-C
• chr10-125807238-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000368797.10(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 ENST00000368797.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.956
• Publications: 30 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: Benign. The variant received -20 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 VariationId is 1273846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368797.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROS	NM_000375.3	MANE Select	c.394+175T>G		intron	N/A	NP_000366.1
	UROS	NM_001324036.2		c.394+175T>G		intron	N/A	NP_001310965.1
	UROS	NM_001324037.2		c.394+175T>G		intron	N/A	NP_001310966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UROS	ENST00000368797.10	TSL:1 MANE Select	c.394+175T>G		intron	N/A	ENSP00000357787.4
	UROS	ENST00000368786.5	TSL:1	c.394+175T>G		intron	N/A	ENSP00000357775.1
	UROS	ENST00000368774.1	TSL:2	c.*167T>G		3_prime_UTR	Exon 6 of 6	ENSP00000357763.1

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

African (AFR) AF: 0.395 AC: 5314 AN: 13452

American (AMR) AF: 0.272 AC: 6509 AN: 23942

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 6098 AN: 15542

East Asian (EAS) AF: 0.331 AC: 10282 AN: 31040

South Asian (SAS) AF: 0.425 AC: 21366 AN: 50306

European-Finnish (FIN) AF: 0.430 AC: 13584 AN: 31602

Middle Eastern (MID) AF: 0.337 AC: 703 AN: 2084

European-Non Finnish (NFE) AF: 0.467 AC: 138400 AN: 296462

Other (OTH) AF: 0.416 AC: 11448 AN: 27538

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

African (AFR) AF: 0.398 AC: 16511 AN: 41488

American (AMR) AF: 0.332 AC: 5066 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1565 AN: 5168

South Asian (SAS) AF: 0.425 AC: 2044 AN: 4812

European-Finnish (FIN) AF: 0.429 AC: 4534 AN: 10572

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31684 AN: 67964

Other (OTH) AF: 0.425 AC: 898 AN: 2112

Alfa AF: 0.437 Hom.: 29042

Bravo AF: 0.412

Asia WGS AF: 0.373 AC: 1298 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.43
DANN	Benign	0.41
PhyloP100		-0.96
PromoterAI		0.0044	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs10510149; hg19: chr10-127495807;