8-28716081-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001440.4(EXTL3):c.22C>T(p.Arg8Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,609,358 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001440.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EXTL3 | NM_001440.4 | c.22C>T | p.Arg8Trp | missense_variant | 3/7 | ENST00000220562.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXTL3 | ENST00000220562.9 | c.22C>T | p.Arg8Trp | missense_variant | 3/7 | 1 | NM_001440.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000524 AC: 13AN: 247886Hom.: 0 AF XY: 0.0000745 AC XY: 10AN XY: 134242
GnomAD4 exome AF: 0.0000597 AC: 87AN: 1457176Hom.: 1 Cov.: 31 AF XY: 0.0000621 AC XY: 45AN XY: 725076
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74350
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2022 | The c.22C>T (p.R8W) alteration is located in exon 3 (coding exon 1) of the EXTL3 gene. This alteration results from a C to T substitution at nucleotide position 22, causing the arginine (R) at amino acid position 8 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 8 of the EXTL3 protein (p.Arg8Trp). This variant is present in population databases (rs780815544, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with EXTL3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1033843). 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: "Possibly Damaging"; 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. - |
Immunoskeletal dysplasia with neurodevelopmental abnormalities Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 08, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at