13-94575086-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGDS	NM_014305.4	c.983-234G>A		intron_variant	Intron 11 of 11	ENST00000261296.7	NP_055120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGDS	ENST00000261296.7	c.983-234G>A		intron_variant	Intron 11 of 11	1	NM_014305.4	ENSP00000261296.5

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

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.696

Alfa AF: 0.672 Hom.: 4296

Bravo AF: 0.704

Asia WGS AF: 0.653 AC: 2261 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.43

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: rs3742107; hg19: chr13-95227340;