17-49990348-CTTTT-CTTTTTT

Variant names:

• chr17-49990348-C-CTT
• rs61087392
• NM_005220.3:c.*1167_*1168dupAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005220.3(DLX3):​c.*1167_*1168dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 139,538 control chromosomes in the GnomAD database, including 462 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.075 (462 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
• Publications: 1 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• 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 (NFE) allele frequency at 95% confidence interval = 0.098 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.*1167_*1168dupAA		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.*1167_*1168dupAA		3_prime_UTR	Exon 3 of 3	ENSP00000389870.2	O60479

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 10427 AN: 139486 Hom.: 462 Cov.: 22

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.00185

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.112

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0903

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

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: 0.0238 AC: 1 AN: 42

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0747 AC: 10426 AN: 139496 Hom.: 462 Cov.: 22 AF XY: 0.0729 AC XY: 4899 AN XY: 67176

African (AFR) AF: 0.0378 AC: 1435 AN: 37944

American (AMR) AF: 0.0662 AC: 918 AN: 13870

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 430 AN: 3328

East Asian (EAS) AF: 0.00186 AC: 9 AN: 4850

South Asian (SAS) AF: 0.0750 AC: 325 AN: 4334

European-Finnish (FIN) AF: 0.0716 AC: 534 AN: 7460

Middle Eastern (MID) AF: 0.106 AC: 29 AN: 274

European-Non Finnish (NFE) AF: 0.100 AC: 6462 AN: 64596

Other (OTH) AF: 0.0898 AC: 176 AN: 1960

Alfa AF: 0.0247 Hom.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs61087392; hg19: chr17-48067712;