Variant 13-94574874-CAAAA-CAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS1

The NM_014305.4(TGDS):c.983-24_983-23delTT variant causes a intron change. The variant allele was found at a frequency of 0.00142 in 966,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0016 ( 0 hom. )

Consequence

TGDS
NM_014305.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.70

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00159 (1374/861600) while in subpopulation AMR AF= 0.00347 (70/20160). AF 95% confidence interval is 0.00282. There are 0 homozygotes in gnomad4_exome. There are 700 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.0000285

AC:

AN:

105272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000863

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000162

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00742

AC:

398

AN:

53648

Hom.:

AF XY:

0.00834

AC XY:

242

AN XY:

29028

show subpopulations

Gnomad AFR exome

AF:

0.00547

Gnomad AMR exome

AF:

0.00873

Gnomad ASJ exome

AF:

0.00860

Gnomad EAS exome

AF:

0.00582

Gnomad SAS exome

AF:

0.00808

Gnomad FIN exome

AF:

0.00516

Gnomad NFE exome

AF:

0.00758

Gnomad OTH exome

AF:

0.00707

GnomAD4 exome

AF:

0.00159

AC:

1374

AN:

861600

Hom.:

AF XY:

0.00162

AC XY:

700

AN XY:

432948

show subpopulations

Gnomad4 AFR exome

AF:

0.000828

Gnomad4 AMR exome

AF:

0.00347

Gnomad4 ASJ exome

AF:

0.00189

Gnomad4 EAS exome

AF:

0.00140

Gnomad4 SAS exome

AF:

0.00282

Gnomad4 FIN exome

AF:

0.00129

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.0000285

AC:

AN:

105272

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

50760

show subpopulations

Gnomad4 AFR

AF:

0.0000458

Gnomad4 AMR

AF:

0.0000863

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000162

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over