rs748047100

Variant names:

• chr13-94574874-CAAAA-C
• rs748047100
• NM_014305.4:c.983-26_983-23delTTTT

Your query was ambiguous. Multiple possible variants found:

• chr13-94574874-CAAAA-C
• chr13-94574874-CAAAA-CA
• chr13-94574874-CAAAA-CAA
• chr13-94574874-CAAAA-CAAA
• chr13-94574874-CAAAA-CAAAAA
• chr13-94574874-CAAAA-CAAAAAA
• chr13-94574874-CAAAA-CAAAAAAA
• chr13-94574874-CAAAA-CAAAAAAAA
• chr13-94574874-CAAAA-CAAAAAAAAAAAAAAAAAAAAAA
• chr13-94574874-CAAAA-CAAAAAAAAAAAAAAAAAAAAAAA
• chr13-94574874-CAAAA-CAAAAAAAAAAAAAAAAAAAAAAAA
• chr13-94574874-CAAAA-CAAAAAAAAAAAAAAAAAAGAAAAAAAAAAAAAAAAAAA
• chr13-94574874-CAAAA-CAAAAAAAAAAAAAAAAAGAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014305.4(TGDS):​c.983-26_983-23delTTTT variant causes a intron change. The variant allele was found at a frequency of 0.00000114 in 875,304 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000011 (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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.983-26_983-23delTTTT		intron	N/A	NP_055120.1	O95455
	TGDS	NM_001304430.2		c.887-26_887-23delTTTT		intron	N/A	NP_001291359.1
	TGDS	NR_130731.2		n.995-26_995-23delTTTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGDS	ENST00000261296.7	TSL:1 MANE Select	c.983-26_983-23delTTTT		intron	N/A	ENSP00000261296.5	O95455
	TGDS	ENST00000953437.1		c.953-26_953-23delTTTT		intron	N/A	ENSP00000623496.1
	TGDS	ENST00000921421.1		c.914-26_914-23delTTTT		intron	N/A	ENSP00000591480.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000114 AC: 1 AN: 875304 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 440070

⚠️ 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: 29250

South Asian (SAS) AF: 0.00 AC: 0 AN: 50696

European-Finnish (FIN) AF: 0.0000352 AC: 1 AN: 28396

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 671614

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 Cov.: 30

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;