rs1060500748
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_000169.3(GLA):c.640-4A>C 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 0.00000418 in 1,195,311 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000169.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLA | NM_000169.3 | c.640-4A>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000218516.4 | |||
RPL36A-HNRNPH2 | NM_001199973.2 | c.300+3493T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLA | ENST00000218516.4 | c.640-4A>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000169.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000889 AC: 1AN: 112477Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34631
GnomAD3 exomes AF: 0.00000545 AC: 1AN: 183379Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67859
GnomAD4 exome AF: 0.00000369 AC: 4AN: 1082834Hom.: 0 Cov.: 29 AF XY: 0.00000286 AC XY: 1AN XY: 349358
GnomAD4 genome ? AF: 0.00000889 AC: 1AN: 112477Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34631
ClinVar
Submissions by phenotype
Fabry disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change falls in intron 4 of the GLA gene. It does not directly change the encoded amino acid sequence of the GLA protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with GLA-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at