17-49990501-C-G

Variant names:

• chr17-49990501-C-G
• rs74607282
• NM_005220.3:c.*1016G>C

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.*1016G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 152,510 control chromosomes in the GnomAD database, including 496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (496 hom., cov: 30)
  • Exomes 𝑓: 0.015 (0 hom.)
• Consequence: DLX3 NM_005220.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.27
• Publications: 5 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=-0.86).
• BP6: Variant 17-49990501-C-G is Benign according to our data. Variant chr17-49990501-C-G is described in ClinVar as Benign. ClinVar VariationId is 324010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 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.*1016G>C		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.*1016G>C		3_prime_UTR	Exon 3 of 3	ENSP00000389870.2	O60479

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9927 AN: 151922 Hom.: 493 Cov.: 30

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0493

GnomAD4 exome AF: 0.0149 AC: 7 AN: 470 Hom.: 0 Cov.: 0 AF XY: 0.0108 AC XY: 3 AN XY: 278

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0157 AC: 7 AN: 446

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.0654 AC: 9948 AN: 152040 Hom.: 496 Cov.: 30 AF XY: 0.0664 AC XY: 4936 AN XY: 74338

African (AFR) AF: 0.114 AC: 4730 AN: 41430

American (AMR) AF: 0.0599 AC: 914 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 114 AN: 3472

East Asian (EAS) AF: 0.162 AC: 838 AN: 5158

South Asian (SAS) AF: 0.134 AC: 646 AN: 4808

European-Finnish (FIN) AF: 0.0124 AC: 131 AN: 10588

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0361 AC: 2457 AN: 68000

Other (OTH) AF: 0.0493 AC: 104 AN: 2110

Alfa AF: 0.0472 Hom.: 27

Bravo AF: 0.0728

Asia WGS AF: 0.150 AC: 523 AN: 3478

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	-0.86
CADD	Benign	0.014
DANN	Benign	0.44
PhyloP100		-2.3
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: rs74607282; hg19: chr17-48067865;