17-28574519-T-G

Variant names:

• chr17-28574519-T-G
• rs569950345
• NM_005165.3:c.599A>C

Variant summary

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

The NM_005165.3(ALDOC):​c.599A>C​(p.Lys200Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,166 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ALDOC NM_005165.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.01

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.599A>C	p.Lys200Thr	missense_variant	Exon 6 of 9	ENST00000226253.9	NP_005156.1
ALDOC	XM_005257949.3	c.599A>C	p.Lys200Thr	missense_variant	Exon 7 of 10		XP_005258006.1
ALDOC	XM_011524556.3	c.599A>C	p.Lys200Thr	missense_variant	Exon 7 of 10		XP_011522858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDOC	ENST00000226253.9	c.599A>C	p.Lys200Thr	missense_variant	Exon 6 of 9	1	NM_005165.3	ENSP00000226253.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74338

Gnomad4 AFR AF: 0.00

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: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	D;D
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.54
Sift	Benign	0.070	T;T
Sift4G	Benign	0.086	T;T
Polyphen		0.061	B;B
Vest4		0.75
MutPred		0.41		Loss of ubiquitination at K200 (P = 0.0103);Loss of ubiquitination at K200 (P = 0.0103);
MVP		0.92
MPC		0.94
ClinPred		0.81	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.60
gMVP		0.75

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

Other links and lift over

dbSNP: rs569950345; hg19: chr17-26901537;