17-49990217-G-C

Position:

• chr17-49990217-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005220.3(DLX3):​c.*1300C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 151,714 control chromosomes in the GnomAD database, including 817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (815 hom., cov: 30)
  • Exomes 𝑓: 0.087 (2 hom.)
• Consequence: DLX3 NM_005220.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.37

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 17-49990217-G-C is Benign according to our data. Variant chr17-49990217-G-C is described in ClinVar as [Benign]. Clinvar id is 324002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX3	NM_005220.3	c.*1300C>G		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	c.*1300C>G		3_prime_UTR_variant	3/3	1	NM_005220.3	ENSP00000389870	P1

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10858 AN: 151520 Hom.: 818 Cov.: 30

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.0968

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0720

GnomAD4 exome AF: 0.0875 AC: 7 AN: 80 Hom.: 2 Cov.: 0 AF XY: 0.0893 AC XY: 5 AN XY: 56

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0716 AC: 10853 AN: 151634 Hom.: 815 Cov.: 30 AF XY: 0.0750 AC XY: 5557 AN XY: 74048

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0520

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.0959

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.0733

Gnomad4 OTH AF: 0.0727

Alfa AF: 0.0639 Hom.: 46

Bravo AF: 0.0672

Asia WGS AF: 0.223 AC: 773 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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- -

Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs3803878; hg19: chr17-48067581;