chr17-28575160-C-T

Variant names:

• chr17-28575160-C-T
• rs761240800
• NM_005165.3:c.287G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005165.3(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. 17/22 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 NM_005165.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.987
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.046392977).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005165.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOC	NM_005165.3	MANE Select	c.287G>A	p.Arg96Gln	missense	Exon 3 of 9	NP_005156.1	P09972

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOC	ENST00000226253.9	TSL:1 MANE Select	c.287G>A	p.Arg96Gln	missense	Exon 3 of 9	ENSP00000226253.4	P09972
	RSKR	ENST00000481916.6	TSL:1	n.*1195+28891G>A		intron	N/A	ENSP00000436369.2	Q96LW2-2
	ALDOC	ENST00000854233.1		c.287G>A	p.Arg96Gln	missense	Exon 3 of 9	ENSP00000524292.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152158 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250808 AF XY: 0.0000221

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 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.: 0 Cov.: 32 AF XY: 0.000127 AC XY: 92 AN XY: 727218

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000149 AC: 166 AN: 1112010

Other (OTH) AF: 0.0000994 AC: 6 AN: 60392

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152158 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74334

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68026

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.0000793

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

EpiCase AF: 0.000218

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	3.6
DANN	Benign	0.85
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.7	N
PhyloP100		0.99
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.99	N
REVEL	Benign	0.17
Sift	Benign	0.86	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.27
MVP		0.45
MPC		0.52
ClinPred		0.034	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.070
gMVP		0.35
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs761240800; hg19: chr17-26902178; COSMIC: COSV52024699; COSMIC: COSV52024699;