chr16-30067318-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001243177.4(ALDOA):c.226C>T(p.Arg76Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000831 in 1,613,434 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R76H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 3 hom. )

Consequence

ALDOA
NM_001243177.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:5

Conservation

PhyloP100: 5.10

Publications

5 publications found

Variant links:

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)

ALDOA links:

LOC112694756 (HGNC:0):

LOC112694756 links:

ENSG00000285043 (HGNC:):

ENSG00000285043 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10859835).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243177.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALDOA	NM_001243177.4	MANE Select	c.226C>T	p.Arg76Cys	missense	Exon 3 of 10	NP_001230106.1	P04075-2
LOC112694756	NM_001365304.2	MANE Select	c.*573C>T		3_prime_UTR	Exon 7 of 14	NP_001352233.1	A0A2U3TZJ4
ALDOA	NM_001127617.2		c.64C>T	p.Arg22Cys	missense	Exon 2 of 9	NP_001121089.1	P04075-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALDOA	ENST00000642816.3	MANE Select	c.226C>T	p.Arg76Cys	missense	Exon 3 of 10	ENSP00000496166.1	P04075-2
ALDOA	ENST00000412304.6	TSL:1	c.64C>T	p.Arg22Cys	missense	Exon 2 of 9	ENSP00000400452.2	P04075-1
ALDOA	ENST00000563060.6	TSL:1	c.64C>T	p.Arg22Cys	missense	Exon 2 of 9	ENSP00000455800.2	P04075-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000195

AC:

AN:

251414

AF XY:

0.000258

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000835

AC:

122

AN:

1461138

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

726872

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00110

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.000387

AC:

AN:

5174

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1112010

Other (OTH)

AF:

0.0000829

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41546

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00166

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0150

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000231

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

HNSHA due to aldolase A deficiency (3)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.86

M_CAP

Benign

0.068

MetaRNN

Benign

0.11

MetaSVM

Uncertain

0.49

MutationAssessor

Pathogenic

3.2

PhyloP100

5.1

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.9

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0010

Sift4G

Benign

0.073

Polyphen

1.0

Vest4

0.72

MVP

0.93

ClinPred

0.19

GERP RS

3.4

PromoterAI

-0.037

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.8

Varity_R

0.63

gMVP

0.76

Mutation Taster

=46/54

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over