Genetic Variant DLX3:c.516+539G>A (chr17-49992861-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005220.3(DLX3):c.516+539G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,064 control chromosomes in the GnomAD database, including 3,039 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3039 hom., cov: 32)

Consequence

DLX3
NM_005220.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00700

Publications

8 publications found

Variant links:

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

DLX3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX3	NM_005220.3 link	c.516+539G>A		intron_variant	Intron 2 of 2	ENST00000434704.2	NP_005211.1	O60479

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX3	ENST00000434704.2 link	c.516+539G>A		intron_variant	Intron 2 of 2	1	NM_005220.3	ENSP00000389870.2		O60479
DLX3	ENST00000512495.2 link	c.156+539G>A		intron_variant	Intron 1 of 1	2		ENSP00000449976.1		F8VXG1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28392

AN:

151946

Hom.:

3040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.187

AC:

28397

AN:

152064

Hom.:

3039

Cov.:

AF XY:

0.191

AC XY:

14221

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.155

AC:

6421

AN:

41484

American (AMR)

AF:

0.143

AC:

2192

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

900

AN:

3468

East Asian (EAS)

AF:

0.488

AC:

2513

AN:

5148

South Asian (SAS)

AF:

0.191

AC:

920

AN:

4810

European-Finnish (FIN)

AF:

0.237

AC:

2512

AN:

10582

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12235

AN:

67974

Other (OTH)

AF:

0.185

AC:

389

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1165

2331

3496

4662

5827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.186

Hom.:

10815

Bravo

AF:

0.179

Asia WGS

AF:

0.311

AC:

1079

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.9

(source)

DANN

Benign

0.53

PhyloP100

0.0070

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over