Variant 17-28575212-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005165.3(ALDOC):c.235T>G(p.Phe79Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALDOC
NM_005165.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Variant links:

Genes affected

ALDOC (HGNC:418): (aldolase, fructose-bisphosphate C) This gene encodes a member of the class I fructose-biphosphate aldolase gene family. Expressed specifically in the hippocampus and Purkinje cells of the brain, the encoded protein is a glycolytic enzyme that catalyzes the reversible aldol cleavage of fructose-1,6-biphosphate and fructose 1-phosphate to dihydroxyacetone phosphate and either glyceraldehyde-3-phosphate or glyceraldehyde, respectively. [provided by RefSeq, Jul 2008]

ALDOC links:

RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

RSKR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ALDOC	NM_005165.3 linkuse as main transcript	c.235T>G	p.Phe79Val	missense_variant	3/9	ENST00000226253.9	NP_005156.1
ALDOC	XM_005257949.3 linkuse as main transcript	c.235T>G	p.Phe79Val	missense_variant	4/10		XP_005258006.1
ALDOC	XM_011524556.3 linkuse as main transcript	c.235T>G	p.Phe79Val	missense_variant	4/10		XP_011522858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDOC	ENST00000226253.9 linkuse as main transcript	c.235T>G	p.Phe79Val	missense_variant	3/9	1	NM_005165.3	ENSP00000226253	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250696

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135528

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727192

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.235T>G (p.F79V) alteration is located in exon 3 (coding exon 2) of the ALDOC gene. This alteration results from a T to G substitution at nucleotide position 235, causing the phenylalanine (F) at amino acid position 79 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.41

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Uncertain

0.53

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

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

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

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.78

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

MetaSVM

Uncertain

0.18

MutationAssessor

Pathogenic

3.6

.;H;H;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.62

N;N;N;.;.;.;N;.

REVEL

Uncertain

0.62

Sift

Uncertain

0.0030

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

Sift4G

Uncertain

0.0020

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

Polyphen

0.64

P;B;B;.;.;.;.;.

Vest4

0.80

MutPred

0.61

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.96

MPC

0.80

ClinPred

0.69

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.80

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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