13-94574874-CAAAA-CAA

Variant names:

• chr13-94574874-CAA-C
• rs748047100
• NM_014305.4:c.983-24_983-23delTT

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70
• Publications: 0 publications found

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGDS	NM_014305.4	MANE Select	c.983-24_983-23delTT		intron	N/A	NP_055120.1	O95455
	TGDS	NM_001304430.2		c.887-24_887-23delTT		intron	N/A	NP_001291359.1
	TGDS	NR_130731.2		n.995-24_995-23delTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGDS	ENST00000261296.7	TSL:1 MANE Select	c.983-24_983-23delTT		intron	N/A	ENSP00000261296.5	O95455
	TGDS	ENST00000953437.1		c.953-24_953-23delTT		intron	N/A	ENSP00000623496.1
	TGDS	ENST00000921421.1		c.914-24_914-23delTT		intron	N/A	ENSP00000591480.1

Frequencies

GnomAD3 genomes AF: 0.0000285 AC: 3 AN: 105272 Hom.: 0 Cov.: 30

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

GnomAD2 exomes AF: 0.00742 AC: 398 AN: 53648 AF XY: 0.00834

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 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.: 0 AF XY: 0.00162 AC XY: 700 AN XY: 432948

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

African (AFR) AF: 0.000828 AC: 15 AN: 18124

American (AMR) AF: 0.00347 AC: 70 AN: 20160

Ashkenazi Jewish (ASJ) AF: 0.00189 AC: 30 AN: 15872

East Asian (EAS) AF: 0.00140 AC: 40 AN: 28672

South Asian (SAS) AF: 0.00282 AC: 139 AN: 49274

European-Finnish (FIN) AF: 0.00129 AC: 36 AN: 27894

Middle Eastern (MID) AF: 0.000336 AC: 1 AN: 2980

European-Non Finnish (NFE) AF: 0.00149 AC: 987 AN: 662102

Other (OTH) AF: 0.00153 AC: 56 AN: 36522

⚠️ 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.

GnomAD4 genome AF: 0.0000285 AC: 3 AN: 105272 Hom.: 0 Cov.: 30 AF XY: 0.0000197 AC XY: 1 AN XY: 50760

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

African (AFR) AF: 0.0000458 AC: 1 AN: 21856

American (AMR) AF: 0.0000863 AC: 1 AN: 11584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2760

East Asian (EAS) AF: 0.00 AC: 0 AN: 4518

South Asian (SAS) AF: 0.00 AC: 0 AN: 3772

European-Finnish (FIN) AF: 0.000162 AC: 1 AN: 6166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52200

Other (OTH) AF: 0.00 AC: 0 AN: 1456

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0232839), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7

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

Other links and lift over

dbSNP: rs748047100; hg19: chr13-95227128;