13-94574884-AAAG-A

Variant names:

• chr13-94574884-AAAG-A
• rs201674028
• NM_014305.4:c.983-35_983-33delCTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014305.4(TGDS):​c.983-35_983-33delCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,260,708 control chromosomes in the GnomAD database, including 13,249 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7320 hom., cov: 0)
  • Exomes 𝑓: 0.18 (5929 hom.)
• Consequence: TGDS NM_014305.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.389
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-94574884-AAAG-A is Benign according to our data. Variant chr13-94574884-AAAG-A is described in ClinVar as Benign. ClinVar VariationId is 1282312.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

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.983-35_983-33delCTT		intron	N/A	NP_055120.1	O95455
	TGDS	NM_001304430.2		c.887-35_887-33delCTT		intron	N/A	NP_001291359.1
	TGDS	NR_130731.2		n.995-35_995-33delCTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGDS	ENST00000261296.7	TSL:1 MANE Select	c.983-35_983-33delCTT		intron	N/A	ENSP00000261296.5	O95455
	TGDS	ENST00000953437.1		c.953-35_953-33delCTT		intron	N/A	ENSP00000623496.1
	TGDS	ENST00000921421.1		c.914-35_914-33delCTT		intron	N/A	ENSP00000591480.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 43737 AN: 148384 Hom.: 7320 Cov.: 0

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.273

GnomAD2 exomes AF: 0.111 AC: 16910 AN: 151682 AF XY: 0.107

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.0653

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.00177

Gnomad FIN exome AF: 0.0881

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.182 AC: 202480 AN: 1112224 Hom.: 5929 AF XY: 0.180 AC XY: 100706 AN XY: 560830

African (AFR) AF: 0.365 AC: 7864 AN: 21560

American (AMR) AF: 0.0840 AC: 2635 AN: 31378

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 3614 AN: 21358

East Asian (EAS) AF: 0.00153 AC: 59 AN: 38572

South Asian (SAS) AF: 0.116 AC: 7910 AN: 68312

European-Finnish (FIN) AF: 0.168 AC: 6693 AN: 39754

Middle Eastern (MID) AF: 0.195 AC: 825 AN: 4234

European-Non Finnish (NFE) AF: 0.195 AC: 164147 AN: 839746

Other (OTH) AF: 0.185 AC: 8733 AN: 47310

GnomAD4 genome AF: 0.295 AC: 43752 AN: 148484 Hom.: 7320 Cov.: 0 AF XY: 0.285 AC XY: 20678 AN XY: 72452

African (AFR) AF: 0.476 AC: 18839 AN: 39566

American (AMR) AF: 0.187 AC: 2832 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 822 AN: 3460

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5180

South Asian (SAS) AF: 0.159 AC: 758 AN: 4758

European-Finnish (FIN) AF: 0.210 AC: 2070 AN: 9834

Middle Eastern (MID) AF: 0.325 AC: 93 AN: 286

European-Non Finnish (NFE) AF: 0.261 AC: 17576 AN: 67300

Other (OTH) AF: 0.273 AC: 566 AN: 2074

Alfa AF: 0.269 Hom.: 413

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs201674028; hg19: chr13-95227138;