17-49990348-CTTTT-CTTTTT

Variant names:

• chr17-49990348-C-CT
• rs61087392
• NM_005220.3:c.*1168dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005220.3(DLX3):​c.*1168dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 139,552 control chromosomes in the GnomAD database, including 171 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (171 hom., cov: 22)
  • Exomes 𝑓: 0.024 (0 hom.)
• Consequence: DLX3 NM_005220.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

Genes affected

DLX3 (HGNC:2916): (distal-less homeobox 3) Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. The Distal-less (Dlx) family of genes comprises at least 6 different members, DLX1-DLX6. Trichodentoosseous syndrome (TDO), an autosomal dominant condition, has been correlated with DLX3 gene mutation. This gene is located in a tail-to-tail configuration with another member of the gene family on the long arm of chromosome 17. Mutations in this gene have been associated with the autosomal dominant conditions trichodentoosseous syndrome and amelogenesis imperfecta with taurodontism. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX3	NM_005220.3	c.*1168dupA		3_prime_UTR_variant	Exon 3 of 3	ENST00000434704.2	NP_005211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX3	ENST00000434704	c.*1168dupA		3_prime_UTR_variant	Exon 3 of 3	1	NM_005220.3	ENSP00000389870.2

Frequencies

GnomAD3 genomes AF: 0.0384 AC: 5352 AN: 139500 Hom.: 173 Cov.: 22

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.0114

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0261

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.0204

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0345

GnomAD4 exome AF: 0.0238 AC: 1 AN: 42 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 28

Gnomad4 FIN exome AF: 0.0238

GnomAD4 genome AF: 0.0384 AC: 5360 AN: 139510 Hom.: 171 Cov.: 22 AF XY: 0.0413 AC XY: 2773 AN XY: 67172

Gnomad4 AFR AF: 0.0642

Gnomad4 AMR AF: 0.0402

Gnomad4 ASJ AF: 0.0261

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0877

Gnomad4 FIN AF: 0.0465

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs61087392; hg19: chr17-48067712;