13-94577852-CTTAAT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014305.4(TGDS):c.825+148_825+152del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 152,198 control chromosomes in the GnomAD database, including 303 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.035 (303 hom., cov: 32)
• Consequence: TGDS NM_014305.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40

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 -10 ACMG points.

• BP6: Variant 13-94577852-CTTAAT-C is Benign according to our data. Variant chr13-94577852-CTTAAT-C is described in ClinVar as [Benign]. Clinvar id is 1266539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGDS	NM_014305.4	c.825+148_825+152del		intron_variant		ENST00000261296.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGDS	ENST00000261296.7	c.825+148_825+152del		intron_variant		1	NM_014305.4	P1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5341 AN: 152080 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0352 AC: 5354 AN: 152198 Hom.: 303 Cov.: 32 AF XY: 0.0345 AC XY: 2571 AN XY: 74424

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0275 Hom.: 16

Bravo AF: 0.0399

Asia WGS AF: 0.00693 AC: 24 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143870920; hg19: chr13-95230106;