NM_000035.4:c.*612A>G

Variant names:

• chr9-101421197-T-C
• rs41296049
• NM_000035.4:c.*612A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000035.4(ALDOB):​c.*612A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0789 in 154,682 control chromosomes in the GnomAD database, including 543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (540 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3 hom.)
• Consequence: ALDOB NM_000035.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.228
• Publications: 1 publications found

Genes affected

ALDOB (HGNC:417): (aldolase, fructose-bisphosphate B) Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a tetrameric glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Vertebrates have 3 aldolase isozymes which are distinguished by their electrophoretic and catalytic properties. Differences indicate that aldolases A, B, and C are distinct proteins, the products of a family of related 'housekeeping' genes exhibiting developmentally regulated expression of the different isozymes. The developing embryo produces aldolase A, which is produced in even greater amounts in adult muscle where it can be as much as 5% of total cellular protein. In adult liver, kidney and intestine, aldolase A expression is repressed and aldolase B is produced. In brain and other nervous tissue, aldolase A and C are expressed about equally. There is a high degree of homology between aldolase A and C. Defects in ALDOB cause hereditary fructose intolerance. [provided by RefSeq, Dec 2008]

ALDOB Gene-Disease associations (from GenCC):

• hereditary fructose intolerance

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 9-101421197-T-C is Benign according to our data. Variant chr9-101421197-T-C is described in ClinVar as Benign. ClinVar VariationId is 364296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000035.4. 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
	ALDOB	NM_000035.4	MANE Select	c.*612A>G		3_prime_UTR	Exon 9 of 9	NP_000026.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOB	ENST00000647789.2	MANE Select	c.*612A>G		3_prime_UTR	Exon 9 of 9	ENSP00000497767.1	P05062
	ALDOB	ENST00000903777.1		c.*612A>G		3_prime_UTR	Exon 9 of 9	ENSP00000573836.1
	ALDOB	ENST00000648064.1		c.*612A>G		downstream_gene	N/A	ENSP00000497990.1	P05062

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12043 AN: 152140 Hom.: 540 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0984

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0908

GnomAD4 exome AF: 0.0697 AC: 169 AN: 2424 Hom.: 3 Cov.: 0 AF XY: 0.0700 AC XY: 92 AN XY: 1314

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.0397 AC: 22 AN: 554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 42

South Asian (SAS) AF: 0.0796 AC: 18 AN: 226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0848 AC: 127 AN: 1498

Other (OTH) AF: 0.0233 AC: 2 AN: 86

GnomAD4 genome AF: 0.0791 AC: 12041 AN: 152258 Hom.: 540 Cov.: 32 AF XY: 0.0782 AC XY: 5821 AN XY: 74438

African (AFR) AF: 0.0365 AC: 1518 AN: 41568

American (AMR) AF: 0.0763 AC: 1166 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 292 AN: 3470

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5174

South Asian (SAS) AF: 0.0989 AC: 477 AN: 4822

European-Finnish (FIN) AF: 0.0642 AC: 681 AN: 10614

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7530 AN: 68004

Other (OTH) AF: 0.0899 AC: 190 AN: 2114

Alfa AF: 0.0890 Hom.: 90

Bravo AF: 0.0775

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary fructosuria (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs41296049; hg19: chr9-104183479;