13-94575086-C-T

Variant names:

• chr13-94575086-C-T
• rs3742107
• NM_014305.4:c.983-234G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014305.4(TGDS):​c.983-234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 151,752 control chromosomes in the GnomAD database, including 37,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (37152 hom., cov: 30)
• Consequence: TGDS NM_014305.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0910
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-94575086-C-T is Benign according to our data. Variant chr13-94575086-C-T is described in ClinVar as Benign. ClinVar VariationId is 1288190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 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.983-234G>A		intron	N/A	NP_055120.1	O95455
	TGDS	NM_001304430.2		c.887-234G>A		intron	N/A	NP_001291359.1
	TGDS	NR_130731.2		n.995-234G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGDS	ENST00000261296.7	TSL:1 MANE Select	c.983-234G>A		intron	N/A	ENSP00000261296.5	O95455
	TGDS	ENST00000953437.1		c.953-234G>A		intron	N/A	ENSP00000623496.1
	TGDS	ENST00000921421.1		c.914-234G>A		intron	N/A	ENSP00000591480.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105229 AN: 151634 Hom.: 37101 Cov.: 30

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.694 AC: 105338 AN: 151752 Hom.: 37152 Cov.: 30 AF XY: 0.695 AC XY: 51509 AN XY: 74138

African (AFR) AF: 0.815 AC: 33752 AN: 41426

American (AMR) AF: 0.730 AC: 11132 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2474 AN: 3468

East Asian (EAS) AF: 0.567 AC: 2929 AN: 5162

South Asian (SAS) AF: 0.668 AC: 3222 AN: 4820

European-Finnish (FIN) AF: 0.655 AC: 6813 AN: 10406

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42670 AN: 67910

Other (OTH) AF: 0.696 AC: 1469 AN: 2110

Alfa AF: 0.678 Hom.: 4561

Bravo AF: 0.704

Asia WGS AF: 0.653 AC: 2261 AN: 3460

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
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.43
PhyloP100		-0.091
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: rs3742107; hg19: chr13-95227340;