rs149460434
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6
The NM_000340.2(SLC2A2):c.593C>T(p.Thr198Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000695 in 1,610,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T198K) has been classified as Likely benign.
Frequency
Consequence
NM_000340.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A2 | NM_000340.2 | c.593C>T | p.Thr198Met | missense_variant | 5/11 | ENST00000314251.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A2 | ENST00000314251.8 | c.593C>T | p.Thr198Met | missense_variant | 5/11 | 1 | NM_000340.2 | P1 | |
ENST00000655926.1 | n.291+12142G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 151974Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000108 AC: 27AN: 250412Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135332
GnomAD4 exome AF: 0.0000651 AC: 95AN: 1458888Hom.: 0 Cov.: 29 AF XY: 0.0000703 AC XY: 51AN XY: 725896
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74352
ClinVar
Submissions by phenotype
Fanconi-Bickel syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 26, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The SLC2A2 p.T198M variant was not identified in the literature but was identified in dbSNP (ID: rs149460434) and ClinVar (classified as uncertain significance by Invitae for Fanconi-Bickel syndrome). The variant was identified in control databases in 28 of 281768 chromosomes at a frequency of 0.00009937 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: South Asian in 7 of 30594 chromosomes (freq: 0.000229), European (non-Finnish) in 20 of 128482 chromosomes (freq: 0.000156) and Latino in 1 of 35248 chromosomes (freq: 0.000028), but was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), or Other populations. The p.T198 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at