13-94574874-CAAAA-CAAA

Variant names:

• chr13-94574874-CA-C
• rs748047100
• NM_014305.4:c.983-23delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014305.4(TGDS):​c.983-23delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 874,594 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (1 hom., cov: 30)
  • Exomes 𝑓: 0.10 (9 hom.)
• Consequence: TGDS NM_014305.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Catel-Manzke syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-94574874-CA-C is Benign according to our data. Variant chr13-94574874-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1244089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00444 (467/105118) while in subpopulation AMR AF = 0.00587 (68/11588). AF 95% confidence interval is 0.0051. There are 1 homozygotes in GnomAd4. There are 237 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014305.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGDS	NM_014305.4	MANE Select	c.983-23delT		intron	N/A	NP_055120.1	O95455
	TGDS	NM_001304430.2		c.887-23delT		intron	N/A	NP_001291359.1
	TGDS	NR_130731.2		n.995-23delT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGDS	ENST00000261296.7	TSL:1 MANE Select	c.983-23delT		intron	N/A	ENSP00000261296.5	O95455
	TGDS	ENST00000953437.1		c.953-23delT		intron	N/A	ENSP00000623496.1
	TGDS	ENST00000921421.1		c.914-23delT		intron	N/A	ENSP00000591480.1

Frequencies

GnomAD3 genomes AF: 0.00442 AC: 465 AN: 105096 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00826

Gnomad AMR AF: 0.00588

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00133

Gnomad SAS AF: 0.00239

Gnomad FIN AF: 0.00848

Gnomad MID AF: 0.00855

Gnomad NFE AF: 0.00562

Gnomad OTH AF: 0.00206

GnomAD2 exomes AF: 0.284 AC: 15253 AN: 53648 AF XY: 0.295

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.305

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.272

Gnomad OTH exome AF: 0.284

GnomAD4 exome AF: 0.100 AC: 77264 AN: 769476 Hom.: 9 Cov.: 11 AF XY: 0.104 AC XY: 39973 AN XY: 383598

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0328 AC: 562 AN: 17140

American (AMR) AF: 0.176 AC: 3010 AN: 17100

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 1672 AN: 13314

East Asian (EAS) AF: 0.170 AC: 3507 AN: 20576

South Asian (SAS) AF: 0.175 AC: 7294 AN: 41792

European-Finnish (FIN) AF: 0.115 AC: 2651 AN: 22994

Middle Eastern (MID) AF: 0.0711 AC: 189 AN: 2658

European-Non Finnish (NFE) AF: 0.0916 AC: 55124 AN: 601916

Other (OTH) AF: 0.102 AC: 3255 AN: 31986

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00444 AC: 467 AN: 105118 Hom.: 1 Cov.: 30 AF XY: 0.00467 AC XY: 237 AN XY: 50700

African (AFR) AF: 0.00128 AC: 28 AN: 21914

American (AMR) AF: 0.00587 AC: 68 AN: 11588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2754

East Asian (EAS) AF: 0.00134 AC: 6 AN: 4492

South Asian (SAS) AF: 0.00240 AC: 9 AN: 3750

European-Finnish (FIN) AF: 0.00848 AC: 52 AN: 6130

Middle Eastern (MID) AF: 0.00943 AC: 2 AN: 212

European-Non Finnish (NFE) AF: 0.00562 AC: 293 AN: 52090

Other (OTH) AF: 0.00205 AC: 3 AN: 1462

Alfa AF: 0.00242 Hom.: 1

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs748047100; hg19: chr13-95227128;