chr4-112377873-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2
The NM_025144.4(ALPK1):c.96C>A(p.Asp32Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_025144.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALPK1 | NM_025144.4 | c.96C>A | p.Asp32Glu | missense_variant | Exon 3 of 16 | ENST00000650871.1 | NP_079420.3 | |
ALPK1 | NM_001102406.2 | c.96C>A | p.Asp32Glu | missense_variant | Exon 3 of 16 | NP_001095876.1 | ||
ALPK1 | NM_001253884.2 | c.17C>A | p.Thr6Lys | missense_variant | Exon 3 of 15 | NP_001240813.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460998Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 726658
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome Uncertain:1
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not provided Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 32 of the ALPK1 protein (p.Asp32Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALPK1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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
Publications
No publications associated with this variant yet.