rs571107777
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015973.5(GAL):c.205G>A(p.Glu69Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,610,834 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 Uncertain significance (★★).
Frequency
Consequence
NM_015973.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAL | NM_015973.5 | c.205G>A | p.Glu69Lys | missense_variant | 4/6 | ENST00000265643.4 | |
LOC107984343 | XR_001748281.1 | n.68-79C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAL | ENST00000265643.4 | c.205G>A | p.Glu69Lys | missense_variant | 4/6 | 1 | NM_015973.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250896Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135712
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1458552Hom.: 0 Cov.: 29 AF XY: 0.0000179 AC XY: 13AN XY: 725780
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74470
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2023 | The c.205G>A (p.E69K) alteration is located in exon 4 (coding exon 3) of the GAL gene. This alteration results from a G to A substitution at nucleotide position 205, causing the glutamic acid (E) at amino acid position 69 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Familial temporal lobe epilepsy 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 16, 2017 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs571107777, ExAC 0.006%) but has not been reported in the literature in individuals with a GAL-related disease. This sequence change replaces glutamic acid with lysine at codon 69 of the GAL protein (p.Glu69Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at