17-28575160-C-T

Position:

chr17-28575160-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000226253.9(ALDOC):c.287G>A(p.Arg96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ALDOC
ENST00000226253.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.987

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:

ALDOC (HGNC:):

ALDOC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046392977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDOC	NM_005165.3 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/9	ENST00000226253.9	NP_005156.1	P09972A0A024QZ64
ALDOC	XM_005257949.3 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	4/10		XP_005258006.1	P09972A0A024QZ64
ALDOC	XM_011524556.3 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	4/10		XP_011522858.1	P09972A0A024QZ64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDOC	ENST00000226253.9 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/9	1	NM_005165.3	ENSP00000226253.4		P09972

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250808

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135530

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:

0.0000618

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000120

AC:

175

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000149

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000132

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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

Aug 02, 2021

The c.287G>A (p.R96Q) alteration is located in exon 3 (coding exon 2) of the ALDOC gene. This alteration results from a G to A substitution at nucleotide position 287, causing the arginine (R) at amino acid position 96 to be replaced by a glutamine (Q). 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

Benign

0.069

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.35

CADD

Benign

3.6

DANN

Benign

0.85

DEOGEN2

Uncertain

0.44

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

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.85

T;.;T;T;T;T;T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.046

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.7

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

MutationTaster

Benign

0.78

D;D;D

PrimateAI

Benign

0.25

PROVEAN

Benign

0.99

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

REVEL

Benign

0.17

Sift

Benign

0.86

T;T;T;.;.;.;T;.

Sift4G

Benign

0.69

T;T;T;T;.;T;.;.

Polyphen

0.0

B;B;B;.;.;.;.;.

Vest4

0.27

MVP

0.45

MPC

0.52

ClinPred

0.034

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.070

gMVP

0.35

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