16-30066961-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001243177.4(ALDOA):c.64T>C(p.Phe22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000966 in 1,552,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

ALDOA
NM_001243177.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17318901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDOA	NM_001243177.4 linkuse as main transcript	c.64T>C	p.Phe22Leu	missense_variant	2/10	ENST00000642816.3
LOC112694756	NM_001365304.2 linkuse as main transcript	c.*489-273T>C		intron_variant		ENST00000338110.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDOA	ENST00000642816.3 linkuse as main transcript	c.64T>C	p.Phe22Leu	missense_variant	2/10		NM_001243177.4		P04075-2
	ENST00000338110.11 linkuse as main transcript	c.*489-273T>C		intron_variant		1	NM_001365304.2	P2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000132

AC:

AN:

151680

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81714

show subpopulations

Gnomad AFR exome

AF:

0.000286

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1399890

Hom.:

Cov.:

AF XY:

0.00000434

AC XY:

AN XY:

690604

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.26e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000322

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000193

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ALDOA-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 05, 2023

The ALDOA c.64T>C variant is predicted to result in the amino acid substitution p.Phe22Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.019% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-30078282-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.76

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Uncertain

0.31

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.15

N;.;N

Sift

Uncertain

0.0070

D;.;D

Sift4G

Pathogenic

0.0

D;.;D

Vest4

0.28

MutPred

0.15

Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);

MVP

0.93

ClinPred

0.23

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.31

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over