NM_000032.5:c.1676G>C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_000032.5(ALAS2):c.1676G>C(p.Arg559Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_000032.5 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALAS2 | NM_000032.5 | c.1676G>C | p.Arg559Pro | missense_variant | Exon 11 of 11 | ENST00000650242.1 | NP_000023.2 | |
ALAS2 | NM_001037968.4 | c.1637G>C | p.Arg546Pro | missense_variant | Exon 11 of 11 | NP_001033057.1 | ||
ALAS2 | NM_001037967.4 | c.1565G>C | p.Arg522Pro | missense_variant | Exon 10 of 10 | NP_001033056.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALAS2 | ENST00000650242.1 | c.1676G>C | p.Arg559Pro | missense_variant | Exon 11 of 11 | NM_000032.5 | ENSP00000497236.1 | |||
ALAS2 | ENST00000396198.7 | c.1637G>C | p.Arg546Pro | missense_variant | Exon 11 of 11 | 5 | ENSP00000379501.3 | |||
ALAS2 | ENST00000335854.8 | c.1565G>C | p.Arg522Pro | missense_variant | Exon 10 of 10 | 2 | ENSP00000337131.4 | |||
ALAS2 | ENST00000498636.1 | c.802G>C | p.Ala268Pro | missense_variant | Exon 5 of 5 | 3 | ENSP00000495662.1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
not provided Pathogenic:1
p.Arg559Pro (CGC>CCC): c.1676 G>C in exon 11 of the ALAS2 gene (NM_000032.4). The R559P missense change likely associated with hereditary X-linked sideroblastic anemia was identified in the ALAS2 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is non-conservative in that a positively charged Arginine residue is replaced by an uncharged Proline residue with a unique ring structure. This change occurs at a position in the ALAS2 protein where a basic amino acid is conserved in mammals. Furthermore, most in-silico analysis models predict that R559P is damaging to the ALAS2 protein. Therefore, R559P is a strong candidate for a disease-causing mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at