Genetic Variant TGDS:c.983-25_983-23dupTTT (chr13-94574874-C-CAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014305.4(TGDS):c.983-25_983-23dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000296 in 980,504 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 0.000047 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TGDS
NM_014305.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Catel-Manzke syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen

TGDS links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014305.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TGDS	NM_014305.4	MANE Select	c.983-25_983-23dupTTT	intron	N/A	NP_055120.1	O95455
TGDS	NM_001304430.2		c.887-25_887-23dupTTT	intron	N/A	NP_001291359.1
TGDS	NR_130731.2		n.995-25_995-23dupTTT	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TGDS	ENST00000261296.7	TSL:1 MANE Select	c.983-23_983-22insTTT	intron	N/A	ENSP00000261296.5	O95455
TGDS	ENST00000953437.1		c.953-23_953-22insTTT	intron	N/A	ENSP00000623496.1
TGDS	ENST00000921421.1		c.914-23_914-22insTTT	intron	N/A	ENSP00000591480.1

Frequencies

GnomAD3 genomes

AF:

0.0000475

AC:

AN:

105304

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

875178

Hom.:

Cov.:

AF XY:

0.0000227

AC XY:

AN XY:

440008

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000384

AC:

AN:

18228

American (AMR)

AF:

0.0000483

AC:

AN:

20710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16230

East Asian (EAS)

AF:

0.0000342

AC:

AN:

29246

South Asian (SAS)

AF:

0.0000395

AC:

AN:

50688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3028

European-Non Finnish (NFE)

AF:

0.00000596

AC:

AN:

671526

Other (OTH)

AF:

0.000242

AC:

AN:

37126

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.306

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000475

AC:

AN:

105326

Hom.:

Cov.:

AF XY:

0.0000394

AC XY:

AN XY:

50820

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000228

AC:

AN:

21922

American (AMR)

AF:

0.00

AC:

AN:

11610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2760

East Asian (EAS)

AF:

0.00

AC:

AN:

4500

South Asian (SAS)

AF:

0.00

AC:

AN:

3750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52198

Other (OTH)

AF:

0.00

AC:

AN:

1466

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0393885), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.385

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Splicing

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

Publications

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13-94574874-CAAAA-CAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over