chr9-101421257-A-T

Variant names:

• chr9-101421257-A-T
• rs41308902
• NM_000035.4:c.*552T>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.*552T>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 0.0804 in 164,460 control chromosomes in the GnomAD database, including 621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (541 hom., cov: 32)
  • Exomes 𝑓: 0.096 (80 hom.)
• Consequence: ALDOB NM_000035.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.99
• 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, 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=-0.79).
• BP6: Variant 9-101421257-A-T is Benign according to our data. Variant chr9-101421257-A-T is described in ClinVar as Benign. ClinVar VariationId is 364298.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.*552T>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.*552T>A		3_prime_UTR	Exon 9 of 9	ENSP00000497767.1	P05062
	ALDOB	ENST00000903777.1		c.*552T>A		3_prime_UTR	Exon 9 of 9	ENSP00000573836.1
	ALDOB	ENST00000648064.1		c.*552T>A		downstream_gene	N/A	ENSP00000497990.1	P05062

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12056 AN: 152182 Hom.: 541 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0907

GnomAD4 exome AF: 0.0959 AC: 1166 AN: 12160 Hom.: 80 Cov.: 0 AF XY: 0.0941 AC XY: 602 AN XY: 6398

African (AFR) AF: 0.0490 AC: 5 AN: 102

American (AMR) AF: 0.0708 AC: 169 AN: 2386

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 9 AN: 104

East Asian (EAS) AF: 0.00291 AC: 2 AN: 688

South Asian (SAS) AF: 0.109 AC: 189 AN: 1736

European-Finnish (FIN) AF: 0.0377 AC: 8 AN: 212

Middle Eastern (MID) AF: 0.125 AC: 4 AN: 32

European-Non Finnish (NFE) AF: 0.116 AC: 739 AN: 6392

Other (OTH) AF: 0.0807 AC: 41 AN: 508

GnomAD4 genome AF: 0.0791 AC: 12054 AN: 152300 Hom.: 541 Cov.: 32 AF XY: 0.0783 AC XY: 5830 AN XY: 74474

African (AFR) AF: 0.0366 AC: 1521 AN: 41570

American (AMR) AF: 0.0764 AC: 1169 AN: 15296

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

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5178

South Asian (SAS) AF: 0.0984 AC: 475 AN: 4828

European-Finnish (FIN) AF: 0.0643 AC: 683 AN: 10620

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

European-Non Finnish (NFE) AF: 0.111 AC: 7537 AN: 68016

Other (OTH) AF: 0.0898 AC: 190 AN: 2116

Alfa AF: 0.0908 Hom.: 87

Bravo AF: 0.0775

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.79
CADD	Benign	7.0
DANN	Benign	0.52
PhyloP100		2.0
Mutation Taster		=99/1	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: rs41308902; hg19: chr9-104183539;