20-46709722-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_030777.4(SLC2A10):c.-15C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,545,498 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_030777.4 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC2A10 | ENST00000359271 | c.-15C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 5 | 1 | NM_030777.4 | ENSP00000352216.2 | |||
SLC2A10 | ENST00000359271 | c.-15C>T | 5_prime_UTR_variant | Exon 1 of 5 | 1 | NM_030777.4 | ENSP00000352216.2 | |||
SLC2A10 | ENST00000486000 | c.-15C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 2 | 3 | ENSP00000478679.1 | ||||
SLC2A10 | ENST00000486000 | c.-15C>T | 5_prime_UTR_variant | Exon 1 of 2 | 3 | ENSP00000478679.1 |
Frequencies
GnomAD3 genomes AF: 0.00168 AC: 255AN: 152130Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.00135 AC: 184AN: 136752Hom.: 1 AF XY: 0.00135 AC XY: 100AN XY: 74220
GnomAD4 exome AF: 0.00182 AC: 2541AN: 1393256Hom.: 5 Cov.: 30 AF XY: 0.00177 AC XY: 1215AN XY: 687248
GnomAD4 genome AF: 0.00167 AC: 255AN: 152242Hom.: 2 Cov.: 33 AF XY: 0.00154 AC XY: 115AN XY: 74442
ClinVar
Submissions by phenotype
not specified Benign:3
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Variant summary: SLC2A10 c.-15C>T is located in the untranslated mRNA region upstream of the initiation codon. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0018 in 1545498 control chromosomes in the gnomAD database (v4.1 dataset), including 7 homozygotes. The observed variant frequency is approximately 1.14 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Arterial Tortuosity Syndrome phenotype (0.0016), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.-15C>T in individuals affected with Arterial Tortuosity Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 139185). Based on the evidence outlined above, the variant was classified as benign. -
Arterial tortuosity syndrome Uncertain:1
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. -
Familial thoracic aortic aneurysm and aortic dissection Benign:1
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not provided Benign:1
SLC2A10: BS2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at