Variant rs545350470 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001243177.4(ALDOA):c.239C>G(p.Pro80Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,452 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ALDOA
NM_001243177.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.86

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 links:

LOC112694756 (HGNC:):

LOC112694756 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDOA	NM_001243177.4 link	c.239C>G	p.Pro80Arg	missense_variant	Exon 3 of 10	ENST00000642816.3	NP_001230106.1	P04075-2
LOC112694756	NM_001365304.2 link	c.*586C>G		3_prime_UTR_variant	Exon 7 of 14	ENST00000338110.11	NP_001352233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDOA	ENST00000642816.3 link	c.239C>G	p.Pro80Arg	missense_variant	Exon 3 of 10		NM_001243177.4	ENSP00000496166.1		P04075-2
ENSG00000285043	ENST00000338110.11 link	c.*586C>G		3_prime_UTR_variant	Exon 7 of 14	1	NM_001365304.2	ENSP00000336927.6		A0A2U3TZJ4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251396

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461452

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

.;T;D;D;D;D;D;.;D;.;D;.;T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;T;.;.;.;D;.;.;D;D;D;.;T;D

M_CAP

Uncertain

0.091

MetaRNN

Uncertain

0.72

D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.64

MutationAssessor

Uncertain

2.8

.;.;M;M;M;.;M;.;M;.;.;.;.;.

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-4.0

.;D;D;D;D;D;D;D;.;.;D;D;D;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0020

.;D;D;D;D;D;D;D;.;.;D;D;D;D

Sift4G

Uncertain

0.041

D;D;D;D;D;D;D;D;.;.;D;D;D;D

Polyphen

0.83

.;.;P;P;P;.;P;.;P;.;.;.;.;.

Vest4

0.67

MutPred

0.60

Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);.;Gain of MoRF binding (P = 0.0026);.;Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);Gain of MoRF binding (P = 0.0026);.;

MVP

0.97

ClinPred

0.87

GERP RS

5.5

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.2

Varity_R

0.58

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over