rs11568531
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_139319.3(SLC17A8):c.355-4C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,594,854 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_139319.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC17A8 | NM_139319.3 | c.355-4C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000323346.10 | |||
SLC17A8 | NM_001145288.2 | c.355-4C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC17A8 | ENST00000323346.10 | c.355-4C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_139319.3 | P1 | |||
SLC17A8 | ENST00000392989.3 | c.355-4C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00633 AC: 964AN: 152180Hom.: 8 Cov.: 31
GnomAD3 exomes AF: 0.00338 AC: 850AN: 251340Hom.: 6 AF XY: 0.00292 AC XY: 397AN XY: 135840
GnomAD4 exome AF: 0.00184 AC: 2649AN: 1442556Hom.: 20 Cov.: 28 AF XY: 0.00179 AC XY: 1288AN XY: 719148
GnomAD4 genome ? AF: 0.00634 AC: 965AN: 152298Hom.: 8 Cov.: 31 AF XY: 0.00565 AC XY: 421AN XY: 74484
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 02, 2018 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | 355-4C>A in Intron 02 of SLC17A8: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 1.7% (62/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs11568531). - |
Autosomal dominant nonsyndromic hearing loss 25 Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 08, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at