chr16-69136806-G-A
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_032830.3(UTP4):c.270G>A(p.Ala90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,140 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0046 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00089 ( 8 hom. )
Consequence
UTP4
NM_032830.3 synonymous
NM_032830.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.184
Genes affected
UTP4 (HGNC:1983): (UTP4 small subunit processome component) This gene encodes a WD40-repeat-containing protein that is localized to the nucleolus. Mutation of this gene causes North American Indian childhood cirrhosis, a severe intrahepatic cholestasis that results in transient neonatal jaundice, and progresses to periportal fibrosis and cirrhosis in childhood and adolescence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 16-69136806-G-A is Benign according to our data. Variant chr16-69136806-G-A is described in ClinVar as [Benign]. Clinvar id is 887042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.184 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UTP4 | NM_032830.3 | c.270G>A | p.Ala90= | synonymous_variant | 3/17 | ENST00000314423.12 | |
UTP4 | NM_001318391.2 | c.21G>A | p.Ala7= | synonymous_variant | 3/17 | ||
UTP4 | XM_047434817.1 | c.270G>A | p.Ala90= | synonymous_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UTP4 | ENST00000314423.12 | c.270G>A | p.Ala90= | synonymous_variant | 3/17 | 1 | NM_032830.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00459 AC: 698AN: 152176Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00143 AC: 359AN: 251496Hom.: 7 AF XY: 0.000964 AC XY: 131AN XY: 135922
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GnomAD4 exome AF: 0.000889 AC: 1300AN: 1461846Hom.: 8 Cov.: 32 AF XY: 0.000804 AC XY: 585AN XY: 727220
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GnomAD4 genome AF: 0.00460 AC: 700AN: 152294Hom.: 4 Cov.: 32 AF XY: 0.00415 AC XY: 309AN XY: 74456
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary North American Indian childhood cirrhosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 16, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at