rs754559092
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_012243.3(SLC35A3):āc.405A>Cā(p.Lys135Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_012243.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC35A3 | NM_012243.3 | c.405A>C | p.Lys135Asn | missense_variant | 4/8 | ENST00000533028.8 | |
LOC124904230 | XR_007066249.1 | n.279+30634T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC35A3 | ENST00000533028.8 | c.405A>C | p.Lys135Asn | missense_variant | 4/8 | 1 | NM_012243.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250694Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135450
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460786Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726688
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74380
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2022 | The c.405A>C (p.K135N) alteration is located in exon 4 (coding exon 3) of the SLC35A3 gene. This alteration results from a A to C substitution at nucleotide position 405, causing the lysine (K) at amino acid position 135 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autism spectrum disorder - epilepsy - arthrogryposis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2021 | This sequence change replaces lysine with asparagine at codon 135 of the SLC35A3 protein (p.Lys135Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs754559092, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with SLC35A3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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