17-28575526-G-T

Position:

• chr17-28575526-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000226253.9(ALDOC):​c.7C>A​(p.His3Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALDOC ENST00000226253.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

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]

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]

ALDOC (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30034548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDOC	NM_005165.3	c.7C>A	p.His3Asn	missense_variant	2/9	ENST00000226253.9	NP_005156.1
ALDOC	XM_005257949.3	c.7C>A	p.His3Asn	missense_variant	3/10		XP_005258006.1
ALDOC	XM_011524556.3	c.7C>A	p.His3Asn	missense_variant	3/10		XP_011522858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDOC	ENST00000226253.9	c.7C>A	p.His3Asn	missense_variant	2/9	1	NM_005165.3	ENSP00000226253.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.7C>A (p.H3N) alteration is located in exon 2 (coding exon 1) of the ALDOC gene. This alteration results from a C to A substitution at nucleotide position 7, causing the histidine (H) at amino acid position 3 to be replaced by an asparagine (N). 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	0.098
BayesDel_addAF	Benign	0.0091	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Benign	0.69
DEOGEN2	Benign	0.30	T;T;T;T;T;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.0053
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	T;.;T;T;T;T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.30	T;T;T;T;T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.5	.;M;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.89	N;N;N;.;.;N;.
REVEL	Benign	0.26
Sift	Benign	0.035	D;D;D;.;.;D;.
Sift4G	Benign	0.22	T;T;T;T;.;.;.
Polyphen		0.0010	B;B;B;.;.;.;.
Vest4		0.35
MutPred		0.23		Gain of glycosylation at P2 (P = 0.1018);Gain of glycosylation at P2 (P = 0.1018);Gain of glycosylation at P2 (P = 0.1018);Gain of glycosylation at P2 (P = 0.1018);Gain of glycosylation at P2 (P = 0.1018);Gain of glycosylation at P2 (P = 0.1018);Gain of glycosylation at P2 (P = 0.1018);
MVP		0.77
MPC		0.49
ClinPred		0.74	D
GERP RS		5.1
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Varity_R		0.78
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-26902544;