chr17-49993514-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005220.3(DLX3):c.402G>A(p.Thr134Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,613,220 control chromosomes in the GnomAD database, including 31,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3009 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28773 hom. )

Consequence

DLX3
NM_005220.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.102

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 17-49993514-C-T is Benign according to our data. Variant chr17-49993514-C-T is described in ClinVar as [Benign]. Clinvar id is 259676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-49993514-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.102 with no splicing effect.

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.402G>A	p.Thr134Thr	synonymous_variant	Exon 2 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.402G>A	p.Thr134Thr	synonymous_variant	Exon 2 of 3	1	NM_005220.3	ENSP00000389870.2		O60479
DLX3	ENST00000512495.2 link	c.42G>A	p.Thr14Thr	synonymous_variant	Exon 1 of 2	2		ENSP00000449976.1		F8VXG1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28235

AN:

151992

Hom.:

3010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.207

AC:

51648

AN:

249274

Hom.:

6571

AF XY:

0.209

AC XY:

28163

AN XY:

135070

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.512

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.184

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.188

AC:

275168

AN:

1461110

Hom.:

28773

Cov.:

AF XY:

0.189

AC XY:

137141

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.498

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.175

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.186

AC:

28240

AN:

152110

Hom.:

3009

Cov.:

AF XY:

0.190

AC XY:

14136

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.258

Gnomad4 EAS

AF:

0.488

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.182

Hom.:

1208

Bravo

AF:

0.178

Asia WGS

AF:

0.311

AC:

1078

AN:

3476

EpiCase

AF:

0.183

EpiControl

AF:

0.181

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

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

- -

Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

Benign:2

Jan 13, 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. -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.26

CADD

Benign

9.6

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over