17-28574719-G-T

Variant names:

• chr17-28574719-G-T
• NM_005165.3:c.517C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005165.3(ALDOC):​c.517C>A​(p.Arg173Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ALDOC NM_005165.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.15

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDOC	NM_005165.3	c.517C>A	p.Arg173Ser	missense_variant	Exon 5 of 9	ENST00000226253.9	NP_005156.1
ALDOC	XM_005257949.3	c.517C>A	p.Arg173Ser	missense_variant	Exon 6 of 10		XP_005258006.1
ALDOC	XM_011524556.3	c.517C>A	p.Arg173Ser	missense_variant	Exon 6 of 10		XP_011522858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDOC	ENST00000226253.9	c.517C>A	p.Arg173Ser	missense_variant	Exon 5 of 9	1	NM_005165.3	ENSP00000226253.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461854 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.90	D;D;D;D;D;.
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;.;D;D;D;D
M_CAP	Pathogenic	0.38	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Pathogenic	4.7	.;H;H;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.5	D;D;D;.;.;.
REVEL	Pathogenic	0.95
Sift	Pathogenic	0.0	D;D;D;.;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D;.;D
Polyphen		0.99	D;D;D;.;.;.
Vest4		0.92
MutPred		0.79		Loss of stability (P = 0.0791);Loss of stability (P = 0.0791);Loss of stability (P = 0.0791);Loss of stability (P = 0.0791);Loss of stability (P = 0.0791);.;
MVP		0.96
MPC		1.4
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.98
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-26901737;