Variant chr13-94574874-C-CAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_014305.4(TGDS):c.983-24_983-23dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 978,304 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0059 ( 5 hom., cov: 30)

Exomes 𝑓: 0.00075 ( 0 hom. )

Consequence

TGDS
NM_014305.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00588 (619/105314) while in subpopulation AFR AF= 0.0261 (572/21914). AF 95% confidence interval is 0.0243. There are 5 homozygotes in gnomad4. There are 302 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGDS	NM_014305.4 link	c.983-24_983-23dupTT		intron_variant	Intron 11 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.983-23_983-22insTT		intron_variant	Intron 11 of 11	1	NM_014305.4	ENSP00000261296.5		O95455

Frequencies

GnomAD3 genomes

AF:

0.00586

AC:

617

AN:

105292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000383

Gnomad OTH

AF:

0.00481

GnomAD3 exomes

AF:

0.00211

AC:

113

AN:

53648

Hom.:

AF XY:

0.00162

AC XY:

AN XY:

29028

show subpopulations

Gnomad AFR exome

AF:

0.0313

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00117

Gnomad EAS exome

AF:

0.000188

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000608

Gnomad NFE exome

AF:

0.000417

Gnomad OTH exome

AF:

0.00354

GnomAD4 exome

AF:

0.000749

AC:

654

AN:

872990

Hom.:

Cov.:

AF XY:

0.000695

AC XY:

305

AN XY:

438886

show subpopulations

Gnomad4 AFR exome

AF:

0.0115

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.000618

Gnomad4 EAS exome

AF:

0.0000686

Gnomad4 SAS exome

AF:

0.000435

Gnomad4 FIN exome

AF:

0.000388

Gnomad4 NFE exome

AF:

0.000470

Gnomad4 OTH exome

AF:

0.00165

GnomAD4 genome

AF:

0.00588

AC:

619

AN:

105314

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

302

AN XY:

50814

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000383

Gnomad4 OTH

AF:

0.00478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over