rs770628227
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_021815.5(SLC5A7):c.119A>C(p.Glu40Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E40K) has been classified as Uncertain significance.
Frequency
Consequence
NM_021815.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC5A7 | NM_021815.5 | c.119A>C | p.Glu40Ala | missense_variant | 2/9 | ENST00000264047.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC5A7 | ENST00000264047.3 | c.119A>C | p.Glu40Ala | missense_variant | 2/9 | 1 | NM_021815.5 | P1 | |
SLC5A7 | ENST00000409059.5 | c.119A>C | p.Glu40Ala | missense_variant | 2/9 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251456Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135908
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461852Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 727224
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2020 | The p.E40A variant (also known as c.119A>C), located in coding exon 1 of the SLC5A7 gene, results from an A to C substitution at nucleotide position 119. The glutamic acid at codon 40 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Neuronopathy, distal hereditary motor, type 7A;C4310694:Congenital myasthenic syndrome 20 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2023 | This variant is present in population databases (rs770628227, gnomAD 0.006%). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 40 of the SLC5A7 protein (p.Glu40Ala). This variant has not been reported in the literature in individuals affected with SLC5A7-related conditions. ClinVar contains an entry for this variant (Variation ID: 532815). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC5A7 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jul 08, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at