NM_000035.4:c.*505C>A

Variant names:

• chr9-101421304-G-T
• rs17772845
• NM_000035.4:c.*505C>A

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.*505C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 220,578 control chromosomes in the GnomAD database, including 873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (542 hom., cov: 32)
  • Exomes 𝑓: 0.085 (331 hom.)
• Consequence: ALDOB NM_000035.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.663
• Publications: 2 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=-0.72).
• BP6: Variant 9-101421304-G-T is Benign according to our data. Variant chr9-101421304-G-T is described in ClinVar as Benign. ClinVar VariationId is 364299.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.*505C>A		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.*505C>A		3_prime_UTR	Exon 9 of 9	ENSP00000497767.1	P05062
	ALDOB	ENST00000903777.1		c.*505C>A		3_prime_UTR	Exon 9 of 9	ENSP00000573836.1
	ALDOB	ENST00000648064.1		c.*505C>A		downstream_gene	N/A	ENSP00000497990.1	P05062

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12056 AN: 152120 Hom.: 542 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0909

GnomAD4 exome AF: 0.0849 AC: 5801 AN: 68340 Hom.: 331 Cov.: 0 AF XY: 0.0860 AC XY: 3100 AN XY: 36056

African (AFR) AF: 0.0400 AC: 80 AN: 2002

American (AMR) AF: 0.0673 AC: 266 AN: 3950

Ashkenazi Jewish (ASJ) AF: 0.0713 AC: 107 AN: 1500

East Asian (EAS) AF: 0.00487 AC: 19 AN: 3898

South Asian (SAS) AF: 0.0942 AC: 972 AN: 10318

European-Finnish (FIN) AF: 0.0604 AC: 156 AN: 2584

Middle Eastern (MID) AF: 0.106 AC: 25 AN: 236

European-Non Finnish (NFE) AF: 0.0963 AC: 3903 AN: 40528

Other (OTH) AF: 0.0821 AC: 273 AN: 3324

GnomAD4 genome AF: 0.0792 AC: 12054 AN: 152238 Hom.: 542 Cov.: 32 AF XY: 0.0783 AC XY: 5831 AN XY: 74428

African (AFR) AF: 0.0366 AC: 1519 AN: 41542

American (AMR) AF: 0.0765 AC: 1170 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 292 AN: 3472

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5190

South Asian (SAS) AF: 0.0984 AC: 475 AN: 4826

European-Finnish (FIN) AF: 0.0643 AC: 681 AN: 10584

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

European-Non Finnish (NFE) AF: 0.111 AC: 7540 AN: 68014

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.0886 Hom.: 119

Bravo AF: 0.0775

Asia WGS AF: 0.0480 AC: 166 AN: 3476

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	-0.72
CADD	Benign	6.8
DANN	Benign	0.80
PhyloP100		0.66
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: rs17772845; hg19: chr9-104183586;