NM_001243177.4:c.1200C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001243177.4(ALDOA):​c.1200C>T​(p.Ser400Ser) 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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.19

Publications

3 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
ALDOANM_001243177.4 linkc.1200C>T p.Ser400Ser synonymous_variant Exon 10 of 10 ENST00000642816.3 NP_001230106.1 P04075-2
LOC112694756NM_001365304.2 linkc.*1547C>T 3_prime_UTR_variant Exon 14 of 14 ENST00000338110.11 NP_001352233.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALDOAENST00000642816.3 linkc.1200C>T p.Ser400Ser synonymous_variant Exon 10 of 10 NM_001243177.4 ENSP00000496166.1 P04075-2
ENSG00000285043ENST00000338110.11 linkc.*1547C>T 3_prime_UTR_variant Exon 14 of 14 1 NM_001365304.2 ENSP00000336927.6 A0A2U3TZJ4

Frequencies

GnomAD3 genomes
AF:
0.0112
AC:
1704
AN:
152186
Hom.:
126
Cov.:
32
show subpopulations
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
GnomAD2 exomes
AF:
0.0269
AC:
6769
AN:
251256
AF XY:
0.0201
show subpopulations
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 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
show subpopulations
African (AFR)
AF:
0.000956
AC:
32
AN:
33480
American (AMR)
AF:
0.178
AC:
7940
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00632
AC:
251
AN:
39700
South Asian (SAS)
AF:
0.000441
AC:
38
AN:
86254
European-Finnish (FIN)
AF:
0.0000562
AC:
3
AN:
53336
Middle Eastern (MID)
AF:
0.000347
AC:
2
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000953
AC:
106
AN:
1112010
Other (OTH)
AF:
0.00440
AC:
266
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.454
Heterozygous variant carriers
0
479
957
1436
1914
2393
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
130
260
390
520
650
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0113
AC:
1715
AN:
152304
Hom.:
128
Cov.:
32
AF XY:
0.0130
AC XY:
967
AN XY:
74482
show subpopulations
African (AFR)
AF:
0.00130
AC:
54
AN:
41552
American (AMR)
AF:
0.104
AC:
1592
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00578
AC:
30
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.0000941
AC:
1
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000191
AC:
13
AN:
68028
Other (OTH)
AF:
0.0118
AC:
25
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
72
144
215
287
359
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00322
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:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

HNSHA due to aldolase A deficiency Benign:3
Nov 15, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Dec 15, 2015
Mayo Clinic Laboratories, Mayo Clinic
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

- -

not specified Benign:1
Feb 03, 2016
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
0.56
DANN
Benign
0.38
PhyloP100
-1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Mutation Taster
=99/1
polymorphism (auto)

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

Other links and lift over

dbSNP: rs77290575; hg19: chr16-30081476; API