rs3803877

Variant names:

• chr17-49990191-A-T
• rs3803877
• NM_005220.3:c.*1326T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005220.3(DLX3):​c.*1326T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 151,878 control chromosomes in the GnomAD database, including 733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (732 hom., cov: 30)
  • Exomes 𝑓: 0.16 (1 hom.)
• Consequence: DLX3 NM_005220.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.90
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 17-49990191-A-T is Benign according to our data. Variant chr17-49990191-A-T is described in ClinVar as Benign. ClinVar VariationId is 324001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 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.*1326T>A		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.*1326T>A		3_prime_UTR	Exon 3 of 3	ENSP00000389870.2	O60479

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13936 AN: 151606 Hom.: 733 Cov.: 30

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0987

GnomAD4 exome AF: 0.162 AC: 25 AN: 154 Hom.: 1 Cov.: 0 AF XY: 0.150 AC XY: 15 AN XY: 100

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.149 AC: 17 AN: 114

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.222 AC: 8 AN: 36

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0918 AC: 13934 AN: 151724 Hom.: 732 Cov.: 30 AF XY: 0.0934 AC XY: 6922 AN XY: 74092

African (AFR) AF: 0.0527 AC: 2180 AN: 41364

American (AMR) AF: 0.0824 AC: 1255 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3464

East Asian (EAS) AF: 0.0965 AC: 495 AN: 5132

South Asian (SAS) AF: 0.0947 AC: 455 AN: 4806

European-Finnish (FIN) AF: 0.136 AC: 1423 AN: 10492

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7249 AN: 67932

Other (OTH) AF: 0.0977 AC: 205 AN: 2098

Alfa AF: 0.103 Hom.: 102

Bravo AF: 0.0856

Asia WGS AF: 0.0960 AC: 335 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs3803877; hg19: chr17-48067555;