16-30067315-C-G

Variant names:

• chr16-30067315-C-G
• rs766734350
• NM_001243177.4:c.223C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001243177.4(ALDOA):​c.223C>G​(p.His75Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 0.0000021 (0 hom.)
• Consequence: ALDOA NM_001243177.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32655245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDOA	NM_001243177.4	c.223C>G	p.His75Asp	missense_variant	Exon 3 of 10	ENST00000642816.3	NP_001230106.1
LOC112694756	NM_001365304.2	c.*570C>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.223C>G	p.His75Asp	missense_variant	Exon 3 of 10		NM_001243177.4	ENSP00000496166.1
ENSG00000285043	ENST00000338110.11	c.*570C>G		3_prime_UTR_variant	Exon 7 of 14	1	NM_001365304.2	ENSP00000336927.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251404 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135900

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461038 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726820

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	.;T;D;D;D;D;D;.;D;.;D;.;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.0068
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D;D;.;.;.;D;.;.;D;D;D;.;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.33	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	0.46	.;.;N;N;N;.;N;.;N;.;.;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	.;N;N;N;N;N;N;N;.;.;N;N;N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0050	.;D;T;T;T;D;T;T;.;.;T;T;D;D
Sift4G	Benign	0.23	T;T;T;T;T;T;T;T;.;.;T;T;T;T
Polyphen		0.0	.;.;B;B;B;.;B;.;B;.;.;.;.;.
Vest4		0.55
MutPred		0.44		Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);.;Gain of disorder (P = 0.0527);.;Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);.;
MVP		0.89
ClinPred		0.23	T
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Varity_R		0.43
gMVP		0.76

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: rs766734350; hg19: chr16-30078636;