11-765066-C-T

Variant names:

• chr11-765066-C-T
• rs2075545
• NM_006755.2:c.*221C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006755.2(TALDO1):​c.*221C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 651,820 control chromosomes in the GnomAD database, including 1,989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (413 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1576 hom.)
• Consequence: TALDO1 NM_006755.2 downstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.235
• Publications: 2 publications found

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: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-765066-C-T is Benign according to our data. Variant chr11-765066-C-T is described in ClinVar as Benign. ClinVar VariationId is 1242856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006755.2. 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
	TALDO1	NM_006755.2	MANE Select	c.*221C>T		downstream_gene	N/A	NP_006746.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TALDO1	ENST00000319006.8	TSL:1 MANE Select	c.*221C>T		downstream_gene	N/A	ENSP00000321259.3
	TALDO1	ENST00000528097.5	TSL:1	c.*274C>T		downstream_gene	N/A	ENSP00000437098.1
	TALDO1	ENST00000530666.1	TSL:2	n.*119C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6278 AN: 152144 Hom.: 409 Cov.: 33

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00376

Gnomad OTH AF: 0.0340

GnomAD4 exome AF: 0.0348 AC: 17375 AN: 499558 Hom.: 1576 Cov.: 6 AF XY: 0.0383 AC XY: 10153 AN XY: 265322

African (AFR) AF: 0.0885 AC: 1251 AN: 14138

American (AMR) AF: 0.00727 AC: 212 AN: 29160

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 194 AN: 15778

East Asian (EAS) AF: 0.263 AC: 7942 AN: 30176

South Asian (SAS) AF: 0.108 AC: 5652 AN: 52526

European-Finnish (FIN) AF: 0.00156 AC: 45 AN: 28932

Middle Eastern (MID) AF: 0.0116 AC: 25 AN: 2150

European-Non Finnish (NFE) AF: 0.00378 AC: 1130 AN: 299088

Other (OTH) AF: 0.0335 AC: 924 AN: 27610

GnomAD4 genome AF: 0.0414 AC: 6305 AN: 152262 Hom.: 413 Cov.: 33 AF XY: 0.0439 AC XY: 3267 AN XY: 74444

African (AFR) AF: 0.0878 AC: 3648 AN: 41526

American (AMR) AF: 0.0176 AC: 269 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3470

East Asian (EAS) AF: 0.272 AC: 1409 AN: 5178

South Asian (SAS) AF: 0.123 AC: 593 AN: 4822

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00376 AC: 256 AN: 68032

Other (OTH) AF: 0.0365 AC: 77 AN: 2110

Alfa AF: 0.0273 Hom.: 28

Bravo AF: 0.0433

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.52
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2075545; hg19: chr11-765066;