chr8-15540383-C-T
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_006765.4(TUSC3):c.-48C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,504,958 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
TUSC3
NM_006765.4 5_prime_UTR
NM_006765.4 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 3.32
Genes affected
TUSC3 (HGNC:30242): (tumor suppressor candidate 3) This gene encodes a protein that has been associated with several biological functions including cellular magnesium uptake, protein glycosylation and embryonic development. This protein localizes to the endoplasmic reticulum and acts as a component of the oligosaccharyl transferase complex which is responsible for N-linked protein glycosylation. This gene is a candidate tumor suppressor gene. Homozygous mutations in this gene are associated with autosomal recessive nonsyndromic mental retardation-7 and in the proliferation and invasiveness of several cancers including metastatic pancreatic cancer, ovarian cancer and glioblastoma multiform. [provided by RefSeq, Oct 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000657 (10/152296) while in subpopulation EAS AF= 0.00194 (10/5150). AF 95% confidence interval is 0.00105. There are 1 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TUSC3 | NM_006765.4 | c.-48C>T | 5_prime_UTR_variant | 1/11 | ENST00000503731.6 | NP_006756.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TUSC3 | ENST00000503731.6 | c.-48C>T | 5_prime_UTR_variant | 1/11 | 1 | NM_006765.4 | ENSP00000424544 | A1 |
Frequencies
GnomAD3 genomes 0.0000657 AC: 10AN: 152182Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000447 AC: 5AN: 111910Hom.: 0 AF XY: 0.0000162 AC XY: 1AN XY: 61562
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GnomAD4 exome AF: 0.0000118 AC: 16AN: 1352662Hom.: 0 Cov.: 31 AF XY: 0.00000903 AC XY: 6AN XY: 664720
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GnomAD4 genome 0.0000657 AC: 10AN: 152296Hom.: 1 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74470
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital disorder of glycosylation Uncertain:1
| Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at