Genetic Variant TALDO1:c.-30C>A (chr11-747452-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000528097.5(TALDO1):c.-30C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,784 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: 34)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

TALDO1
ENST00000528097.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.970

Publications

1 publications found

Variant links:

Genes affected

TALDO1 (HGNC:11559): (transaldolase 1) Transaldolase 1 is a key enzyme of the nonoxidative pentose phosphate pathway providing ribose-5-phosphate for nucleic acid synthesis and NADPH for lipid biosynthesis. This pathway can also maintain glutathione at a reduced state and thus protect sulfhydryl groups and cellular integrity from oxygen radicals. The functional gene of transaldolase 1 is located on chromosome 11 and a pseudogene is identified on chromosome 1 but there are conflicting map locations. The second and third exon of this gene were developed by insertion of a retrotransposable element. This gene is thought to be involved in multiple sclerosis. [provided by RefSeq, Jul 2008]

TALDO1 Gene-Disease associations (from GenCC):

transaldolase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

TALDO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000528097.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TALDO1	NM_006755.2	MANE Select	c.-30C>A		upstream_gene	N/A	NP_006746.1	A0A140VK56

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TALDO1	ENST00000528097.5	TSL:1	c.-30C>A	5_prime_UTR	Exon 1 of 8	ENSP00000437098.1	F2Z393
TALDO1	ENST00000896396.1		c.-30C>A	5_prime_UTR	Exon 1 of 9	ENSP00000566455.1
TALDO1	ENST00000933599.1		c.-30C>A	5_prime_UTR	Exon 1 of 8	ENSP00000603658.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.38e-7

AC:

AN:

1355784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

672094

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

27758

American (AMR)

AF:

0.00

AC:

AN:

34552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23528

East Asian (EAS)

AF:

0.00

AC:

AN:

31872

South Asian (SAS)

AF:

0.00

AC:

AN:

77392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5584

European-Non Finnish (NFE)

AF:

9.51e-7

AC:

AN:

1051580

Other (OTH)

AF:

0.00

AC:

AN:

56050

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.3

(source)

DANN

Benign

0.58

PhyloP100

-0.97

PromoterAI

-0.069

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over