Variant 13-94574860-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014305.4(TGDS):c.983-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00081 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TGDS
NM_014305.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002981

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.340

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 13-94574860-G-A is Benign according to our data. Variant chr13-94574860-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 720702.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGDS	NM_014305.4 linkuse as main transcript	c.983-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261296.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGDS	ENST00000261296.7 linkuse as main transcript	c.983-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014305.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

130058

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000128

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000319

Gnomad OTH

AF:

0.000562

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000812

AC:

1035

AN:

1274026

Hom.:

Cov.:

AF XY:

0.000868

AC XY:

551

AN XY:

634722

show subpopulations

Gnomad4 AFR exome

AF:

0.00110

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00158

Gnomad4 EAS exome

AF:

0.00235

Gnomad4 SAS exome

AF:

0.00270

Gnomad4 FIN exome

AF:

0.000881

Gnomad4 NFE exome

AF:

0.000583

Gnomad4 OTH exome

AF:

0.000763

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000123

AC:

AN:

130120

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

AN XY:

62790

show subpopulations

Gnomad4 AFR

AF:

0.000322

Gnomad4 AMR

AF:

0.000151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000128

Gnomad4 NFE

AF:

0.0000319

Gnomad4 OTH

AF:

0.000556

Alfa

AF:

0.000169

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

Cadd

Benign

7.6

Dann

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000030

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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