chr13-94574874-C-CAAAAAAAAAAAAAAAAAAA

Variant names:

• chr13-94574874-C-CAAAAAAAAAAAAAAAAAAA
• rs748047100
• NM_014305.4:c.983-23_983-22insTTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_014305.4(TGDS):​c.983-23_983-22insTTTTTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TGDS NM_014305.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• 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.983-23_983-22insTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_055120.1	O95455
	TGDS	NM_001304430.2		c.887-23_887-22insTTTTTTTTTTTTTTTTTTT		intron	N/A	NP_001291359.1
	TGDS	NR_130731.2		n.995-23_995-22insTTTTTTTTTTTTTTTTTTT		intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 105302 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

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: 0.00000114 AC: 1 AN: 875330 Hom.: 0 Cov.: 11 AF XY: 0.00000227 AC XY: 1 AN XY: 440094

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

African (AFR) AF: 0.00 AC: 0 AN: 18236

American (AMR) AF: 0.00 AC: 0 AN: 20712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16230

East Asian (EAS) AF: 0.00 AC: 0 AN: 29252

South Asian (SAS) AF: 0.00 AC: 0 AN: 50702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3030

European-Non Finnish (NFE) AF: 0.00000149 AC: 1 AN: 671630

Other (OTH) AF: 0.00 AC: 0 AN: 37140

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 105302 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 50776

African (AFR) AF: 0.00 AC: 0 AN: 21854

American (AMR) AF: 0.00 AC: 0 AN: 11592

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: 0.00 AC: 0 AN: 6182

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52206

Other (OTH) AF: 0.00 AC: 0 AN: 1458

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

Other links and lift over

dbSNP: rs748047100; hg19: chr13-95227128;