NM_005220.3:c.138C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005220.3(DLX3):c.138C>T(p.Pro46Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,614,156 control chromosomes in the GnomAD database, including 5,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 929 hom., cov: 34)

Exomes 𝑓: 0.059 ( 4454 hom. )

Consequence

DLX3
NM_005220.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.174

Publications

7 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 17-49994861-G-A is Benign according to our data. Variant chr17-49994861-G-A is described in ClinVar as Benign. ClinVar VariationId is 259675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.174 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX3	NM_005220.3 link	c.138C>T	p.Pro46Pro	synonymous_variant	Exon 1 of 3	ENST00000434704.2	NP_005211.1	O60479

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX3	ENST00000434704.2 link	c.138C>T	p.Pro46Pro	synonymous_variant	Exon 1 of 3	1	NM_005220.3	ENSP00000389870.2		O60479

Frequencies

GnomAD3 genomes

AF:

0.0859

AC:

13069

AN:

152166

Hom.:

927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0812

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.0133

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0405

Gnomad OTH

AF:

0.0632

GnomAD2 exomes

AF:

0.0859

AC:

21594

AN:

251386

AF XY:

0.0850

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.0260

Gnomad EAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.0390

Gnomad OTH exome

AF:

0.0629

GnomAD4 exome

AF:

0.0588

AC:

86024

AN:

1461872

Hom.:

4454

Cov.:

AF XY:

0.0616

AC XY:

44768

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.167

AC:

5606

AN:

33480

American (AMR)

AF:

0.128

AC:

5747

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

707

AN:

26136

East Asian (EAS)

AF:

0.197

AC:

7834

AN:

39700

South Asian (SAS)

AF:

0.181

AC:

15582

AN:

86256

European-Finnish (FIN)

AF:

0.0181

AC:

964

AN:

53404

Middle Eastern (MID)

AF:

0.0560

AC:

323

AN:

5768

European-Non Finnish (NFE)

AF:

0.0407

AC:

45251

AN:

1112010

Other (OTH)

AF:

0.0664

AC:

4010

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

5571

11142

16714

22285

27856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2078

4156

6234

8312

10390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0860

AC:

13098

AN:

152284

Hom.:

929

Cov.:

AF XY:

0.0871

AC XY:

6487

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.164

AC:

6820

AN:

41562

American (AMR)

AF:

0.0813

AC:

1244

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

114

AN:

3470

East Asian (EAS)

AF:

0.179

AC:

926

AN:

5170

South Asian (SAS)

AF:

0.194

AC:

935

AN:

4822

European-Finnish (FIN)

AF:

0.0133

AC:

141

AN:

10622

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0405

AC:

2752

AN:

68022

Other (OTH)

AF:

0.0658

AC:

139

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

590

1180

1769

2359

2949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0564

Hom.:

692

Bravo

AF:

0.0953

Asia WGS

AF:

0.205

AC:

715

AN:

3478

EpiCase

AF:

0.0391

EpiControl

AF:

0.0374

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tricho-dento-osseous syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.17

PromoterAI

0.013

Neutral

(source)

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over