17-28575212-A-G

Variant names:

• chr17-28575212-A-G
• rs766767014
• NM_005165.3:c.235T>C

Variant summary

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

The NM_005165.3(ALDOC):​c.235T>C​(p.Phe79Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALDOC NM_005165.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.51

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]

ACMG classification

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
ALDOC	NM_005165.3	c.235T>C	p.Phe79Leu	missense_variant	Exon 3 of 9	ENST00000226253.9	NP_005156.1
ALDOC	XM_005257949.3	c.235T>C	p.Phe79Leu	missense_variant	Exon 4 of 10		XP_005258006.1
ALDOC	XM_011524556.3	c.235T>C	p.Phe79Leu	missense_variant	Exon 4 of 10		XP_011522858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDOC	ENST00000226253.9	c.235T>C	p.Phe79Leu	missense_variant	Exon 3 of 9	1	NM_005165.3	ENSP00000226253.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Uncertain	0.44	T;D;D;T;T;.;.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.057
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.53	T;.;T;T;T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.36	.;N;N;.;.;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	1.3	N;N;N;.;.;.;N;.
REVEL	Uncertain	0.39
Sift	Benign	1.0	T;T;T;.;.;.;T;.
Sift4G	Benign	1.0	T;T;T;T;.;T;.;.
Polyphen		0.0020	B;B;B;.;.;.;.;.
Vest4		0.66
MutPred		0.62		Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);.;Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);
MVP		0.94
MPC		0.52
ClinPred		0.90	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.40
gMVP		0.85

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

Other links and lift over

dbSNP: rs766767014; hg19: chr17-26902230;