rs1553201582
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PM2PP3_StrongPP5_Moderate
The NM_012243.3(SLC35A3):c.342+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,419,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_012243.3 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC35A3 | NM_012243.3 | c.342+1G>A | splice_donor_variant | ENST00000533028.8 | |||
LOC124904230 | XR_007066249.1 | n.279+38314C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC35A3 | ENST00000533028.8 | c.342+1G>A | splice_donor_variant | 1 | NM_012243.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 7.04e-7 AC: 1AN: 1419496Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0AN XY: 705866
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autism spectrum disorder - epilepsy - arthrogryposis syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2023 | ClinVar contains an entry for this variant (Variation ID: 541613). This variant has not been reported in the literature in individuals affected with SLC35A3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the SLC35A3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC35A3 are known to be pathogenic (PMID: 24031089, 28328131). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at