chr16-30067276-C-G

Variant names:

• chr16-30067276-C-G
• rs1163749559
• NM_001243177.4:c.184C>G

Variant summary

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

The NM_001243177.4(ALDOA):​c.184C>G​(p.Leu62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,214 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: ALDOA NM_001243177.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

Genes affected

ALDOA (HGNC:414): (aldolase, fructose-bisphosphate A) This gene encodes a member of the class I fructose-bisphosphate aldolase protein family. The encoded protein is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Three aldolase isozymes (A, B, and C), encoded by three different genes, are differentially expressed during development. Mutations in this gene have been associated with Glycogen Storage Disease XII, an autosomal recessive disorder associated with hemolytic anemia. Disruption of this gene also plays a role in the progression of multiple types of cancers. Related pseudogenes have been identified on chromosomes 3 and 10. [provided by RefSeq, Sep 2017]

LOC112694756 (HGNC:):

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
ALDOA	NM_001243177.4	c.184C>G	p.Leu62Val	missense_variant	Exon 3 of 10	ENST00000642816.3	NP_001230106.1
LOC112694756	NM_001365304.2	c.*531C>G		3_prime_UTR_variant	Exon 7 of 14	ENST00000338110.11	NP_001352233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDOA	ENST00000642816.3	c.184C>G	p.Leu62Val	missense_variant	Exon 3 of 10		NM_001243177.4	ENSP00000496166.1
ENSG00000285043	ENST00000338110.11	c.*531C>G		3_prime_UTR_variant	Exon 7 of 14	1	NM_001365304.2	ENSP00000336927.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74366

Gnomad4 AFR AF: 0.0000241

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: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	.;T;D;D;D;T;D;.;D;.;T;.;T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D;D;.;.;.;D;.;.;D;D;D;.;D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Pathogenic	3.4	.;.;M;M;M;.;M;.;M;.;.;.;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	.;N;N;N;N;N;N;N;.;.;N;N;N;N
REVEL	Uncertain	0.56
Sift	Uncertain	0.016	.;D;D;D;D;D;D;D;.;.;D;D;D;D
Sift4G	Benign	0.061	T;T;T;T;T;T;T;D;.;.;T;T;T;D
Polyphen		0.16	.;.;B;B;B;.;B;.;B;.;.;.;.;.
Vest4		0.58
MutPred		0.44		Loss of stability (P = 0.0999);Loss of stability (P = 0.0999);Loss of stability (P = 0.0999);Loss of stability (P = 0.0999);Loss of stability (P = 0.0999);Loss of stability (P = 0.0999);Loss of stability (P = 0.0999);.;Loss of stability (P = 0.0999);.;Loss of stability (P = 0.0999);Loss of stability (P = 0.0999);Loss of stability (P = 0.0999);.;
MVP		0.92
ClinPred		0.96	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.49
gMVP		0.74

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: rs1163749559; hg19: chr16-30078597;