16-30064516-AG-A

Variant names:

• chr16-30064516-AG-A
• rs964620994
• ENST00000412304.6:c.-286delG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001127617.2(ALDOA):​c.-286delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALDOA NM_001127617.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617
• Publications: 0 publications found

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]

ALDOA Gene-Disease associations (from GenCC):

• glycogen storage disease due to aldolase A deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)

LOC112694756 (HGNC:0):

ENSG00000285043 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127617.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC112694756	NM_001365304.2	MANE Select	c.*488+15delG		intron	N/A	NP_001352233.1	A0A2U3TZJ4
	ALDOA	NM_001127617.2		c.-286delG		5_prime_UTR	Exon 1 of 9	NP_001121089.1	P04075-1
	ALDOA	NM_184043.2		c.-22+15delG		intron	N/A	NP_908932.1	V9HWN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOA	ENST00000412304.6	TSL:1	c.-286delG		5_prime_UTR	Exon 1 of 9	ENSP00000400452.2	P04075-1
	ENSG00000285043	ENST00000338110.11	TSL:1 MANE Select	c.*488+15delG		intron	N/A	ENSP00000336927.6	A0A2U3TZJ4
	ALDOA	ENST00000563060.6	TSL:1	c.-22+15delG		intron	N/A	ENSP00000455800.2	P04075-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 246362 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124848

African (AFR) AF: 0.00 AC: 0 AN: 7182

American (AMR) AF: 0.00 AC: 0 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9240

East Asian (EAS) AF: 0.00 AC: 0 AN: 22896

South Asian (SAS) AF: 0.00 AC: 0 AN: 3036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158078

Other (OTH) AF: 0.00 AC: 0 AN: 16374

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs964620994; hg19: chr16-30075837;