9-101421603-G-T

Variant names:

• chr9-101421603-G-T
• rs17772869
• NM_000035.4:c.*206C>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.*206C>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 0.0886 in 633,154 control chromosomes in the GnomAD database, including 2,961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (525 hom., cov: 32)
  • Exomes 𝑓: 0.093 (2436 hom.)
• Consequence: ALDOB NM_000035.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.341
• Publications: 4 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=-0.83).
• BP6: Variant 9-101421603-G-T is Benign according to our data. Variant chr9-101421603-G-T is described in ClinVar as Benign. ClinVar VariationId is 364303.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.*206C>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.*206C>A		3_prime_UTR	Exon 9 of 9	ENSP00000497767.1	P05062
	ALDOB	ENST00000648064.1		c.*206C>A		3_prime_UTR	Exon 9 of 9	ENSP00000497990.1	P05062
	ALDOB	ENST00000903775.1		c.*206C>A		3_prime_UTR	Exon 10 of 10	ENSP00000573834.1

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11299 AN: 152144 Hom.: 525 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0747

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0982

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0875

GnomAD4 exome AF: 0.0932 AC: 44822 AN: 480892 Hom.: 2436 Cov.: 4 AF XY: 0.0950 AC XY: 24363 AN XY: 256322

African (AFR) AF: 0.0201 AC: 280 AN: 13900

American (AMR) AF: 0.0593 AC: 1752 AN: 29562

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 1351 AN: 15830

East Asian (EAS) AF: 0.00287 AC: 85 AN: 29566

South Asian (SAS) AF: 0.106 AC: 5608 AN: 52658

European-Finnish (FIN) AF: 0.0717 AC: 2443 AN: 34062

Middle Eastern (MID) AF: 0.127 AC: 265 AN: 2082

European-Non Finnish (NFE) AF: 0.111 AC: 30585 AN: 276552

Other (OTH) AF: 0.0919 AC: 2453 AN: 26680

GnomAD4 genome AF: 0.0742 AC: 11294 AN: 152262 Hom.: 525 Cov.: 32 AF XY: 0.0736 AC XY: 5477 AN XY: 74450

African (AFR) AF: 0.0192 AC: 800 AN: 41574

American (AMR) AF: 0.0746 AC: 1140 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0842 AC: 292 AN: 3466

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5186

South Asian (SAS) AF: 0.0987 AC: 476 AN: 4822

European-Finnish (FIN) AF: 0.0643 AC: 682 AN: 10602

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7535 AN: 68006

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0996 Hom.: 1093

Bravo AF: 0.0720

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hereditary fructosuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		-0.34
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: rs17772869; hg19: chr9-104183885; COSMIC: COSV107493550; COSMIC: COSV107493550;