rs11302

Variant names:

• chr11-764414-A-G
• rs11302
• NM_006755.2:c.962A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-764414-A-G
• chr11-764414-A-C
• chr11-764414-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006755.2(TALDO1):​c.962A>G​(p.Lys321Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00564 in 1,611,302 control chromosomes in the GnomAD database, including 73 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 (19 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (54 hom.)
• Consequence: TALDO1 NM_006755.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 6.61
• Publications: 11 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: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.015927285).
• BP6: Variant 11-764414-A-G is Benign according to our data. Variant chr11-764414-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 306139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.011 (1643/149452) while in subpopulation AFR AF = 0.028 (1160/41384). AF 95% confidence interval is 0.0267. There are 19 homozygotes in GnomAd4. There are 769 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TALDO1	NM_006755.2	MANE Select	c.962A>G	p.Lys321Arg	missense	Exon 7 of 8	NP_006746.1	A0A140VK56

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TALDO1	ENST00000319006.8	TSL:1 MANE Select	c.962A>G	p.Lys321Arg	missense	Exon 7 of 8	ENSP00000321259.3	P37837-1
	TALDO1	ENST00000528097.5	TSL:1	c.*1A>G		3_prime_UTR	Exon 7 of 8	ENSP00000437098.1	F2Z393
	TALDO1	ENST00000896396.1		c.1025A>G	p.Lys342Arg	missense	Exon 8 of 9	ENSP00000566455.1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1641 AN: 149332 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00343

Gnomad ASJ AF: 0.0370

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.000865

Gnomad MID AF: 0.0197

Gnomad NFE AF: 0.00399

Gnomad OTH AF: 0.00988

GnomAD2 exomes AF: 0.00550 AC: 1380 AN: 251106 AF XY: 0.00479

Gnomad AFR exome AF: 0.0283

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.0347

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.00366

Gnomad OTH exome AF: 0.00523

GnomAD4 exome AF: 0.00509 AC: 7444 AN: 1461850 Hom.: 54 Cov.: 32 AF XY: 0.00490 AC XY: 3563 AN XY: 727226

African (AFR) AF: 0.0294 AC: 983 AN: 33480

American (AMR) AF: 0.00257 AC: 115 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0327 AC: 854 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00118 AC: 102 AN: 86256

European-Finnish (FIN) AF: 0.000468 AC: 25 AN: 53416

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.00436 AC: 4844 AN: 1111984

Other (OTH) AF: 0.00811 AC: 490 AN: 60392

GnomAD4 genome AF: 0.0110 AC: 1643 AN: 149452 Hom.: 19 Cov.: 33 AF XY: 0.0105 AC XY: 769 AN XY: 73066

African (AFR) AF: 0.0280 AC: 1160 AN: 41384

American (AMR) AF: 0.00342 AC: 51 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 126 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4796

European-Finnish (FIN) AF: 0.000865 AC: 9 AN: 10400

Middle Eastern (MID) AF: 0.0211 AC: 6 AN: 284

European-Non Finnish (NFE) AF: 0.00399 AC: 264 AN: 66146

Other (OTH) AF: 0.00978 AC: 20 AN: 2046

Alfa AF: 0.00692 Hom.: 15

Bravo AF: 0.0118

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.0313 AC: 138

ESP6500EA AF: 0.00651 AC: 56

ExAC AF: 0.00545 AC: 662

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00496

EpiControl AF: 0.00510

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Deficiency of transaldolase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.016	T
MetaSVM	Uncertain	-0.040	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.037	D
Polyphen		0.69	P
Vest4		0.54
MVP		0.94
MPC		0.30
ClinPred		0.041	T
GERP RS		4.1
Varity_R		0.49
gMVP		0.64
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11302; hg19: chr11-764414; COSMIC: COSV59797634; COSMIC: COSV59797634;