Variant 17-49990191-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005220.3(DLX3):c.*1326T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 151,878 control chromosomes in the GnomAD database, including 733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 732 hom., cov: 30)

Exomes 𝑓: 0.16 ( 1 hom. )

Consequence

DLX3
NM_005220.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.90

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 17-49990191-A-T is Benign according to our data. Variant chr17-49990191-A-T is described in ClinVar as [Benign]. Clinvar id is 324001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 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.*1326T>A		3_prime_UTR_variant	3/3	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.*1326T>A		3_prime_UTR_variant	3/3	1	NM_005220.3	ENSP00000389870	P1

Frequencies

GnomAD3 genomes

AF:

0.0919

AC:

13936

AN:

151606

Hom.:

733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0527

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0825

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0966

Gnomad SAS

AF:

0.0954

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.0987

GnomAD4 exome

AF:

0.162

AC:

AN:

154

Hom.:

Cov.:

AF XY:

0.150

AC XY:

AN XY:

100

show subpopulations

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0918

AC:

13934

AN:

151724

Hom.:

732

Cov.:

AF XY:

0.0934

AC XY:

6922

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.0527

Gnomad4 AMR

AF:

0.0824

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.0965

Gnomad4 SAS

AF:

0.0947

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.0977

Alfa

AF:

0.103

Hom.:

102

Bravo

AF:

0.0856

Asia WGS

AF:

0.0960

AC:

335

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.79

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