17-49990191-A-T

Position:

• chr17-49990191-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.90

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 -14 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_single_submitter, 1 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	UniProt
DLX3	NM_005220.3	c.*1326T>A		3_prime_UTR_variant	3/3	ENST00000434704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLX3	ENST00000434704.2	c.*1326T>A		3_prime_UTR_variant	3/3	1	NM_005220.3	P1

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13936 AN: 151606 Hom.: 733 Cov.: 30

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: 25 AN: 154 Hom.: 1 Cov.: 0 AF XY: 0.150 AC XY: 15 AN XY: 100

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.: 30 AF XY: 0.0934 AC XY: 6922 AN XY: 74092

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	12
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

Other links and lift over

dbSNP: rs3803877; hg19: chr17-48067555;