8-28716123-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001440.4(EXTL3):c.64C>T(p.Arg22Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R22H) 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.64C>T | p.Arg22Cys | missense_variant | 3/7 | ENST00000220562.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EXTL3 | ENST00000220562.9 | c.64C>T | p.Arg22Cys | missense_variant | 3/7 | 1 | NM_001440.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251032Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135730
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461340Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727004
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 22 of the EXTL3 protein (p.Arg22Cys). This variant is present in population databases (rs754077651, gnomAD 0.008%). 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: 1487985). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EXTL3 protein function. 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