NM_024740.2:c.694G>C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_024740.2(ALG9):āc.694G>Cā(p.Ala232Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000445 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024740.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALG9 | ENST00000616540.5 | c.694G>C | p.Ala232Pro | missense_variant | Exon 6 of 15 | 1 | NM_024740.2 | ENSP00000482437.1 | ||
ENSG00000258529 | ENST00000622211.4 | c.1393G>C | p.Ala465Pro | missense_variant | Exon 10 of 19 | 2 | ENSP00000482396.1 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000289 AC: 72AN: 249556Hom.: 0 AF XY: 0.000281 AC XY: 38AN XY: 135398
GnomAD4 exome AF: 0.000456 AC: 666AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.000440 AC XY: 320AN XY: 727230
GnomAD4 genome AF: 0.000341 AC: 52AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74468
ClinVar
Submissions by phenotype
not provided Uncertain:3
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Reported in the heterozygous state in a patient with kidney and liver cysts in published literature (PMID: 31395617); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 31395617, 27391121) -
ALG9 congenital disorder of glycosylation Uncertain:2
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 232 of the ALG9 protein (p.Ala232Pro). This variant is present in population databases (rs36111204, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of ALG9-related conditions (PMID: 27391121, 31395617). ClinVar contains an entry for this variant (Variation ID: 96135). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ALG9 function (PMID: 31395617). 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. -
Gillessen-Kaesbach-Nishimura syndrome;C2931006:ALG9 congenital disorder of glycosylation Uncertain:1
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See cases Benign:1
ACMG classification criteria: PM2, BP1, BP4 -
Autosomal dominant polycystic liver disease Benign:1
Variant able to rescue ALG9 knockout effect on Polycystin-1 maturation in vitro -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at