chr16-5071868-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_019109.5(ALG1):c.19G>C(p.Val7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,604,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. V7I) has been classified as Likely benign.
Frequency
Consequence
NM_019109.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG1 | NM_019109.5 | c.19G>C | p.Val7Leu | missense_variant | 1/13 | ENST00000262374.10 | |
ALG1 | XM_017023457.3 | c.19G>C | p.Val7Leu | missense_variant | 1/12 | ||
ALG1 | XR_007064892.1 | n.26G>C | non_coding_transcript_exon_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG1 | ENST00000262374.10 | c.19G>C | p.Val7Leu | missense_variant | 1/13 | 1 | NM_019109.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000432 AC: 1AN: 231674Hom.: 0 AF XY: 0.00000787 AC XY: 1AN XY: 127112
GnomAD4 exome AF: 0.00000620 AC: 9AN: 1452734Hom.: 0 Cov.: 31 AF XY: 0.00000830 AC XY: 6AN XY: 722760
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74390
ClinVar
Submissions by phenotype
ALG1-congenital disorder of glycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2021 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 7 of the ALG1 protein (p.Val7Leu). This variant is present in population databases (rs199891552, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with ALG1-related conditions. 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 ALG1 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