2-233768333-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_007120.3(UGT1A4):c.1201A>G(p.Asn401Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_007120.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UGT1A4 | NM_007120.3 | c.1201A>G | p.Asn401Asp | missense_variant | Exon 4 of 5 | ENST00000373409.8 | NP_009051.1 | |
UGT1A5 | NM_019078.2 | c.1201A>G | p.Asn401Asp | missense_variant | Exon 4 of 5 | ENST00000373414.4 | NP_061951.1 | |
UGT1A3 | NM_019093.4 | c.1201A>G | p.Asn401Asp | missense_variant | Exon 4 of 5 | ENST00000482026.6 | NP_061966.1 | |
UGT1A1 | NM_000463.3 | c.1198A>G | p.Asn400Asp | missense_variant | Exon 4 of 5 | ENST00000305208.10 | NP_000454.1 | |
UGT1A6 | NM_001072.4 | c.1195A>G | p.Asn399Asp | missense_variant | Exon 4 of 5 | ENST00000305139.11 | NP_001063.2 | |
UGT1A10 | NM_019075.4 | c.1189A>G | p.Asn397Asp | missense_variant | Exon 4 of 5 | ENST00000344644.10 | NP_061948.1 | |
UGT1A8 | NM_019076.5 | c.1189A>G | p.Asn397Asp | missense_variant | Exon 4 of 5 | ENST00000373450.5 | NP_061949.3 | |
UGT1A7 | NM_019077.3 | c.1189A>G | p.Asn397Asp | missense_variant | Exon 4 of 5 | ENST00000373426.4 | NP_061950.2 | |
UGT1A9 | NM_021027.3 | c.1189A>G | p.Asn397Asp | missense_variant | Exon 4 of 5 | ENST00000354728.5 | NP_066307.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UGT1A4 | ENST00000373409.8 | c.1201A>G | p.Asn401Asp | missense_variant | Exon 4 of 5 | 1 | NM_007120.3 | ENSP00000362508.4 | ||
UGT1A5 | ENST00000373414.4 | c.1201A>G | p.Asn401Asp | missense_variant | Exon 4 of 5 | 1 | NM_019078.2 | ENSP00000362513.3 | ||
UGT1A3 | ENST00000482026.6 | c.1201A>G | p.Asn401Asp | missense_variant | Exon 4 of 5 | 1 | NM_019093.4 | ENSP00000418532.1 | ||
UGT1A1 | ENST00000305208.10 | c.1198A>G | p.Asn400Asp | missense_variant | Exon 4 of 5 | 1 | NM_000463.3 | ENSP00000304845.5 | ||
UGT1A6 | ENST00000305139.11 | c.1195A>G | p.Asn399Asp | missense_variant | Exon 4 of 5 | 1 | NM_001072.4 | ENSP00000303174.6 | ||
UGT1A10 | ENST00000344644.10 | c.1189A>G | p.Asn397Asp | missense_variant | Exon 4 of 5 | 1 | NM_019075.4 | ENSP00000343838.5 | ||
UGT1A9 | ENST00000354728.5 | c.1189A>G | p.Asn397Asp | missense_variant | Exon 4 of 5 | 1 | NM_021027.3 | ENSP00000346768.4 | ||
UGT1A7 | ENST00000373426.4 | c.1189A>G | p.Asn397Asp | missense_variant | Exon 4 of 5 | 1 | NM_019077.3 | ENSP00000362525.3 | ||
UGT1A8 | ENST00000373450.5 | c.1189A>G | p.Asn397Asp | missense_variant | Exon 4 of 5 | 1 | NM_019076.5 | ENSP00000362549.4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249052Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134818
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461894Hom.: 0 Cov.: 36 AF XY: 0.00000825 AC XY: 6AN XY: 727248
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
Crigler-Najjar syndrome, type II Pathogenic:1
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not specified Uncertain:1
Variant summary: UGT1A1 c.1198A>G (p.Asn400Asp) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 249052 control chromosomes. c.1198A>G has been reported in the literature in a homozugous individual affected with UGT1A1-Related Disorders who was also homozygous for the UGT1A1*37 aka c.-40_-43dupTATA promoter expansion variant, which is likely pathogenic but not sufficient to explain the more severe presentation in this individual (example, Labrune_2002). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 12402338). The following publication has been ascertained in the context of this evaluation (PMID: 12402338). ClinVar contains an entry for this variant (Variation ID: 12286). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. -
Gilbert syndrome Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at