Variant rs754214510 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014305.4(TGDS):c.286C>A(p.Leu96Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TGDS
NM_014305.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGDS	NM_014305.4 linkuse as main transcript	c.286C>A	p.Leu96Ile	missense_variant	4/12	ENST00000261296.7	NP_055120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGDS	ENST00000261296.7 linkuse as main transcript	c.286C>A	p.Leu96Ile	missense_variant	4/12	1	NM_014305.4	ENSP00000261296	P1
TGDS	ENST00000498294.5 linkuse as main transcript	n.468C>A		non_coding_transcript_exon_variant	4/8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000930

AC:

AN:

215050

Hom.:

AF XY:

0.00

AC XY:

AN XY:

117338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000865

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1422412

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706902

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.037

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.50

MutationAssessor

Benign

-0.61

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.70

REVEL

Uncertain

0.30

Sift

Benign

0.15

Sift4G

Benign

0.43

Polyphen

0.34

Vest4

0.62

MutPred

0.49

Gain of methylation at K91 (P = 0.0499);

MVP

0.62

MPC

0.39

ClinPred

0.33

GERP RS

5.5

Varity_R

0.096

gMVP

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over