chr16-30067586-A-G
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001243177.4(ALDOA):āc.411A>Gā(p.Thr137Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000716 in 1,613,782 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0035 ( 3 hom., cov: 32)
Exomes š: 0.00043 ( 5 hom. )
Consequence
ALDOA
NM_001243177.4 synonymous
NM_001243177.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.65
Genes affected
ALDOA (HGNC:414): (aldolase, fructose-bisphosphate A) This gene encodes a member of the class I fructose-bisphosphate aldolase protein family. The encoded protein is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Three aldolase isozymes (A, B, and C), encoded by three different genes, are differentially expressed during development. Mutations in this gene have been associated with Glycogen Storage Disease XII, an autosomal recessive disorder associated with hemolytic anemia. Disruption of this gene also plays a role in the progression of multiple types of cancers. Related pseudogenes have been identified on chromosomes 3 and 10. [provided by RefSeq, Sep 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 16-30067586-A-G is Benign according to our data. Variant chr16-30067586-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 382578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30067586-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-3.64 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALDOA | NM_001243177.4 | c.411A>G | p.Thr137Thr | synonymous_variant | 4/10 | ENST00000642816.3 | NP_001230106.1 | |
LOC112694756 | NM_001365304.2 | c.*758A>G | 3_prime_UTR_variant | 8/14 | ENST00000338110.11 | NP_001352233.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALDOA | ENST00000642816.3 | c.411A>G | p.Thr137Thr | synonymous_variant | 4/10 | NM_001243177.4 | ENSP00000496166.1 | |||
ENSG00000285043 | ENST00000338110.11 | c.*758A>G | 3_prime_UTR_variant | 8/14 | 1 | NM_001365304.2 | ENSP00000336927.6 |
Frequencies
GnomAD3 genomes AF: 0.00345 AC: 524AN: 151832Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000935 AC: 235AN: 251416Hom.: 1 AF XY: 0.000721 AC XY: 98AN XY: 135902
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GnomAD4 exome AF: 0.000432 AC: 631AN: 1461832Hom.: 5 Cov.: 32 AF XY: 0.000424 AC XY: 308AN XY: 727212
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GnomAD4 genome AF: 0.00346 AC: 525AN: 151950Hom.: 3 Cov.: 32 AF XY: 0.00325 AC XY: 241AN XY: 74264
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 19, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 15, 2017 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
HNSHA due to aldolase A deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 27, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 27, 2024 | - - |
ALDOA-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 08, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at