13-94574885-AAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014305.4(TGDS):c.983-35_983-34del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 812,838 control chromosomes in the GnomAD database, including 181 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (150 hom., cov: 0)
  • Exomes 𝑓: 0.013 (31 hom.)
• Consequence: TGDS NM_014305.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.670

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-94574885-AAG-A is Benign according to our data. Variant chr13-94574885-AAG-A is described in ClinVar as [Benign]. Clinvar id is 1228958.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGDS	NM_014305.4	c.983-35_983-34del		intron_variant		ENST00000261296.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGDS	ENST00000261296.7	c.983-35_983-34del		intron_variant		1	NM_014305.4	P1

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 3580 AN: 79980 Hom.: 150 Cov.: 0

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00244

Gnomad MID AF: 0.0145

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.0375

GnomAD4 exome AF: 0.0130 AC: 9559 AN: 732790 Hom.: 31 AF XY: 0.0126 AC XY: 4660 AN XY: 371018

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.00692

Gnomad4 ASJ exome AF: 0.00832

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.00566

Gnomad4 FIN exome AF: 0.00763

Gnomad4 NFE exome AF: 0.0118

Gnomad4 OTH exome AF: 0.0167

GnomAD4 genome AF: 0.0447 AC: 3582 AN: 80048 Hom.: 150 Cov.: 0 AF XY: 0.0432 AC XY: 1726 AN XY: 39946

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00244

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.0371

Alfa AF: 0.0211 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs58691634; hg19: chr13-95227139;