17-49990292-TAAA-TAAAA

Variant names:

• chr17-49990292-T-TA
• rs3840066
• NM_005220.3:c.*1224dupT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

DLX3 Gene-Disease associations (from GenCC):

• tricho-dento-osseous syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005220.3. 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
	DLX3	NM_005220.3	MANE Select	c.*1224dupT		3_prime_UTR	Exon 3 of 3	NP_005211.1	O60479

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX3	ENST00000434704.2	TSL:1 MANE Select	c.*1224dupT		3_prime_UTR	Exon 3 of 3	ENSP00000389870.2	O60479

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0585 AC: 2238 AN: 38278

American (AMR) AF: 0.00958 AC: 134 AN: 13992

Ashkenazi Jewish (ASJ) AF: 0.00623 AC: 21 AN: 3372

East Asian (EAS) AF: 0.00343 AC: 17 AN: 4952

South Asian (SAS) AF: 0.00111 AC: 5 AN: 4490

European-Finnish (FIN) AF: 0.00413 AC: 32 AN: 7750

Middle Eastern (MID) AF: 0.00730 AC: 2 AN: 274

European-Non Finnish (NFE) AF: 0.00278 AC: 180 AN: 64734

Other (OTH) AF: 0.0151 AC: 29 AN: 1926

Alfa AF: 0.000205 Hom.: 12

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Amelogenesis Imperfecta, Dominant (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3840066; hg19: chr17-48067656;