16-30067586-A-C

Variant names:

• chr16-30067586-A-C
• rs76767223
• NM_001243177.4:c.411A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001243177.4(ALDOA):​c.411A>C​(p.Thr137Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T137T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALDOA NM_001243177.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65
• Publications: 1 publications found

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]

ALDOA Gene-Disease associations (from GenCC):

• glycogen storage disease due to aldolase A deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

LOC112694756 (HGNC:0):

ENSG00000285043 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-3.64 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243177.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOA	NM_001243177.4	MANE Select	c.411A>C	p.Thr137Thr	synonymous	Exon 4 of 10	NP_001230106.1
	LOC112694756	NM_001365304.2	MANE Select	c.*758A>C		3_prime_UTR	Exon 8 of 14	NP_001352233.1
	ALDOA	NM_001127617.2		c.249A>C	p.Thr83Thr	synonymous	Exon 3 of 9	NP_001121089.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDOA	ENST00000642816.3	MANE Select	c.411A>C	p.Thr137Thr	synonymous	Exon 4 of 10	ENSP00000496166.1
	ALDOA	ENST00000412304.6	TSL:1	c.249A>C	p.Thr83Thr	synonymous	Exon 3 of 9	ENSP00000400452.2
	ALDOA	ENST00000563060.6	TSL:1	c.249A>C	p.Thr83Thr	synonymous	Exon 3 of 9	ENSP00000455800.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.36
DANN	Benign	0.70
PhyloP100		-3.6
PromoterAI		0.0023	Neutral

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

Other links and lift over

dbSNP: rs76767223; hg19: chr16-30078907;