rs387906338
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM4_SupportingPP5_Very_Strong
The NM_013339.4(ALG6):c.897_899delAAT(p.Ile299del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000268 in 1,606,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_013339.4 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251236Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135832
GnomAD4 exome AF: 0.0000254 AC: 37AN: 1454202Hom.: 0 AF XY: 0.0000221 AC XY: 16AN XY: 724014
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74370
ClinVar
Submissions by phenotype
ALG6-congenital disorder of glycosylation 1C Pathogenic:4
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This variant, c.897_899del, results in the deletion of 1 amino acid(s) of the ALG6 protein (p.Ile299del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753111873, gnomAD 0.006%). This variant has been observed in individual(s) with congenital disorder of glycosylation 1c (PMID: 10924277, 27287710). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 30420). For these reasons, this variant has been classified as Pathogenic. -
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not provided Pathogenic:4
In-frame deletion of one amino acid in a non-repeat region; Commonly identified and reported variant in patients with CDG-Ic (Hanefeld et al., 2000; Sun et al., 2005; Morava et al., 2006); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10924277, 21811164, 10832578, 12855228, 16007612, 27287710, 27535533) -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at