chrX-101407775-G-A
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000169.3(GLA):c.129C>T(p.Gly43Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,209,678 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 38 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000169.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000232 AC: 26AN: 112191Hom.: 0 Cov.: 23 AF XY: 0.000262 AC XY: 9AN XY: 34343
GnomAD3 exomes AF: 0.000463 AC: 85AN: 183430Hom.: 0 AF XY: 0.000354 AC XY: 24AN XY: 67872
GnomAD4 exome AF: 0.000107 AC: 117AN: 1097435Hom.: 0 Cov.: 31 AF XY: 0.0000799 AC XY: 29AN XY: 362797
GnomAD4 genome AF: 0.000232 AC: 26AN: 112243Hom.: 0 Cov.: 23 AF XY: 0.000262 AC XY: 9AN XY: 34405
ClinVar
Submissions by phenotype
not specified Benign:4
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proposed classification - variant undergoing re-assessment, contact laboratory -
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not provided Benign:4
Variant summary: The GLA c.129C>T (p.Gly43Gly) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not affect any ESE site. This variant was found in 30/87749 control chromosomes in ExAC database, including 7 hemizygotes (~1 in 4179 males, assuming male/female ratio is 1). Fabry disease affects an estimated 1 in 40,000 to 60,000 males (https://ghr.nlm.nih.gov/condition/fabry-disease#statistics), which is much lower than the hemizygote frequency of the variant of interest. Therefore, this variant is unlikely to associate with the disease. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -
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Fabry disease Benign:3
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at