rs33937843

Positions:

chr17-49994861-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000434704.2(DLX3):c.138C>T(p.Pro46=) 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
ENST00000434704.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.174

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 -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 id is 259675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-49994861-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
DLX3	NM_005220.3 linkuse as main transcript	c.138C>T	p.Pro46=	synonymous_variant	1/3	ENST00000434704.2	NP_005211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX3	ENST00000434704.2 linkuse as main transcript	c.138C>T	p.Pro46=	synonymous_variant	1/3	1	NM_005220.3	ENSP00000389870	P1

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

GnomAD3 exomes

AF:

0.0859

AC:

21594

AN:

251386

Hom.:

1524

AF XY:

0.0850

AC XY:

11555

AN XY:

135900

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 SAS exome

AF:

0.181

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

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.0271

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.0181

Gnomad4 NFE exome

AF:

0.0407

Gnomad4 OTH exome

AF:

0.0664

GnomAD4 genome

AF:

0.0860

AC:

13098

AN:

152284

Hom.:

929

Cov.:

AF XY:

0.0871

AC XY:

6487

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.0813

Gnomad4 ASJ

AF:

0.0329

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.0133

Gnomad4 NFE

AF:

0.0405

Gnomad4 OTH

AF:

0.0658

Alfa

AF:

0.0583

Hom.:

220

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Tricho-dento-osseous syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

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

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