rs77290575

chr16-30070155-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001243177.4(ALDOA):c.1200C>T(p.Ser400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00641 in 1,614,104 control chromosomes in the GnomAD database, including 944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (128 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (816 hom.)
• Consequence: ALDOA NM_001243177.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.19

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 16-30070155-C-T is Benign according to our data. Variant chr16-30070155-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 318839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALDOA	NM_001243177.4	c.1200C>T	p.Ser400=	synonymous_variant	10/10	ENST00000642816.3
LOC112694756	NM_001365304.2	c.*1547C>T		3_prime_UTR_variant	14/14	ENST00000338110.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDOA	ENST00000642816.3	c.1200C>T	p.Ser400=	synonymous_variant	10/10		NM_001243177.4
	ENST00000338110.11	c.*1547C>T		3_prime_UTR_variant	14/14	1	NM_001365304.2	P2

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1704 AN: 152186 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00596

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0269 AC: 6769 AN: 251256 Hom.: 694 AF XY: 0.0201 AC XY: 2726 AN XY: 135864

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00511

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.0148

GnomAD4 exome AF: 0.00591 AC: 8638 AN: 1461800 Hom.: 816 Cov.: 33 AF XY: 0.00491 AC XY: 3574 AN XY: 727196

Gnomad4 AFR exome AF: 0.000956

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00632

Gnomad4 SAS exome AF: 0.000441

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000953

Gnomad4 OTH exome AF: 0.00440

GnomAD4 genome AF: 0.0113 AC: 1715 AN: 152304 Hom.: 128 Cov.: 32 AF XY: 0.0130 AC XY: 967 AN XY: 74482

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00578

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00323 Hom.: 17

Bravo AF: 0.0200

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

HNSHA due to aldolase A deficiency Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 03, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Dec 15, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.56
Dann	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

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: rs77290575; hg19: chr16-30081476;