10-125785806-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01
Variant links:
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]

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ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
UROSXM_017016612.3 linkc.694A>C p.Met232Leu missense_variant Exon 10 of 10 XP_016872101.1
UROSXM_011540127.3 linkc.661-546A>C intron_variant Intron 9 of 9 XP_011538429.1
UROSNR_136677.2 linkn.950A>C non_coding_transcript_exon_variant Exon 10 of 11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UROSENST00000622016.4 linkc.274A>C p.Met92Leu missense_variant Exon 4 of 4 5 ENSP00000483041.1 A0A087X021
UROSENST00000616800.4 linkc.160-546A>C intron_variant Intron 2 of 2 5 ENSP00000482520.1 A0A087WZB7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10901431; hg19: chr10-127474375; API