Variant chr13-94577481-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014305.4(TGDS):c.826-52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,452,096 control chromosomes in the GnomAD database, including 2,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 1114 hom., cov: 32)

Exomes 𝑓: 0.024 ( 1109 hom. )

Consequence

TGDS
NM_014305.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.800

Variant links:

Genes affected

TGDS (HGNC:20324): (TDP-glucose 4,6-dehydratase) The protein encoded by this gene is a member of the short-chain dehydrogenases/reductases (SDR) superfamily, and is thought to contain a nicotinamide adenine dinucleotide (NAD) binding domain. This large SDR family of enzymes is involved in the metabolism of a variety of compounds, including prostaglandins, retinoids, lipids, steroid hormones, and xenobiotics. Mutations in this gene have been associated with Catel-Manzke syndrome, which is characterized by Pierre Robin sequence, and radial deviation of the index finger due to the presence of an accessory bone between the index finger and its proximal phalanx. Pierre Robin sequence is defined by an undersized jaw, backwards displacement of the tongue base that causes an obstruction of the airways, and can also be associated with a cleft palate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

TGDS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 13-94577481-A-G is Benign according to our data. Variant chr13-94577481-A-G is described in ClinVar as [Benign]. Clinvar id is 1260430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGDS	NM_014305.4 link	c.826-52T>C		intron_variant	Intron 9 of 11	ENST00000261296.7	NP_055120.1	O95455

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGDS	ENST00000261296.7 link	c.826-52T>C		intron_variant	Intron 9 of 11	1	NM_014305.4	ENSP00000261296.5		O95455

Frequencies

GnomAD3 genomes

AF:

0.0782

AC:

11891

AN:

152126

Hom.:

1114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0440

Gnomad ASJ

AF:

0.0158

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0161

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0208

Gnomad OTH

AF:

0.0712

GnomAD3 exomes

AF:

0.0317

AC:

5680

AN:

179066

Hom.:

362

AF XY:

0.0271

AC XY:

2672

AN XY:

98506

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.0234

Gnomad ASJ exome

AF:

0.0161

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0114

Gnomad FIN exome

AF:

0.0134

Gnomad NFE exome

AF:

0.0196

Gnomad OTH exome

AF:

0.0290

GnomAD4 exome

AF:

0.0239

AC:

31007

AN:

1299852

Hom.:

1109

Cov.:

AF XY:

0.0232

AC XY:

15060

AN XY:

648834

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.0281

Gnomad4 ASJ exome

AF:

0.0141

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.0196

Gnomad4 OTH exome

AF:

0.0333

GnomAD4 genome

AF:

0.0782

AC:

11909

AN:

152244

Hom.:

1114

Cov.:

AF XY:

0.0744

AC XY:

5537

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.0440

Gnomad4 ASJ

AF:

0.0158

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0160

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.0208

Gnomad4 OTH

AF:

0.0704

Alfa

AF:

0.0448

Hom.:

Bravo

AF:

0.0856

Asia WGS

AF:

0.0210

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over