17-49990292-T-TA

Position:

• chr17-49990292-T-TA

Variant summary

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

The NM_005220.3(DLX3):​c.*1224dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 140,660 control chromosomes in the GnomAD database, including 68 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (68 hom., cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLX3 NM_005220.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.62

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 (AFR) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX3	NM_005220.3	c.*1224dupT		3_prime_UTR_variant	3/3	ENST00000434704.2	NP_005211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX3	ENST00000434704	c.*1224dupT		3_prime_UTR_variant	3/3	1	NM_005220.3	ENSP00000389870.2

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2650 AN: 140630 Hom.: 68 Cov.: 28

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00952

Gnomad ASJ AF: 0.00623

Gnomad EAS AF: 0.00342

Gnomad SAS AF: 0.00111

Gnomad FIN AF: 0.00413

Gnomad MID AF: 0.00676

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.0152

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0189 AC: 2658 AN: 140660 Hom.: 68 Cov.: 28 AF XY: 0.0185 AC XY: 1256 AN XY: 67930

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.00958

Gnomad4 ASJ AF: 0.00623

Gnomad4 EAS AF: 0.00343

Gnomad4 SAS AF: 0.00111

Gnomad4 FIN AF: 0.00413

Gnomad4 NFE AF: 0.00278

Gnomad4 OTH AF: 0.0151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Amelogenesis Imperfecta, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs3840066; hg19: chr17-48067656;