13-94574860-G-A

Position:

• chr13-94574860-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000261296.7(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 ENST00000261296.7 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

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 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	Protein	UniProt
TGDS	NM_014305.4	c.983-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261296.7	NP_055120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGDS	ENST00000261296.7	c.983-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014305.4	ENSP00000261296	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 16 AN: 130058 Hom.: 0 Cov.: 31 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.: 0 Cov.: 22 AF XY: 0.000868 AC XY: 551 AN XY: 634722

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: 16 AN: 130120 Hom.: 0 Cov.: 31 AF XY: 0.000159 AC XY: 10 AN XY: 62790

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

Other links and lift over

dbSNP: rs1447520086; hg19: chr13-95227114;