16-30064516-AG-AGG

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001127617.2(ALDOA):​c.-286dupG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 398,724 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: ALDOA NM_001127617.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 16-30064516-A-AG is Benign according to our data. Variant chr16-30064516-A-AG is described in ClinVar as Likely_benign. ClinVar VariationId is 513850.Status of the report is criteria_provided_single_submitter, 1 stars.

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+15dupG		intron	N/A	NP_001352233.1	A0A2U3TZJ4
	ALDOA	NM_001127617.2		c.-286dupG		5_prime_UTR	Exon 1 of 9	NP_001121089.1	P04075-1
	ALDOA	NM_184043.2		c.-22+15dupG		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.-286dupG		5_prime_UTR	Exon 1 of 9	ENSP00000400452.2	P04075-1
	ENSG00000285043	ENST00000338110.11	TSL:1 MANE Select	c.*488+15dupG		intron	N/A	ENSP00000336927.6	A0A2U3TZJ4
	ALDOA	ENST00000563060.6	TSL:1	c.-22+15dupG		intron	N/A	ENSP00000455800.2	P04075-1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152244 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000649 AC: 16 AN: 246362 Hom.: 0 Cov.: 0 AF XY: 0.0000320 AC XY: 4 AN XY: 124848

African (AFR) AF: 0.000139 AC: 1 AN: 7182

American (AMR) AF: 0.00202 AC: 15 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 AF: 0.000177 AC: 27 AN: 152362 Hom.: 1 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74512

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.00176 AC: 27 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000518

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

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;