17-49990589-T-C

Position:

• chr17-49990589-T-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.*928A>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 0.722 in 152,440 control chromosomes in the GnomAD database, including 41,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (41670 hom., cov: 30)
  • Exomes 𝑓: 0.87 (177 hom.)
• Consequence: DLX3 NM_005220.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.600

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=-0.75).
• BP6: Variant 17-49990589-T-C is Benign according to our data. Variant chr17-49990589-T-C is described in ClinVar as [Benign]. Clinvar id is 324013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX3	NM_005220.3	c.*928A>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.*928A>G		3_prime_UTR_variant	3/3	1	NM_005220.3	ENSP00000389870	P1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109563 AN: 151862 Hom.: 41664 Cov.: 30

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.753

GnomAD4 exome AF: 0.874 AC: 402 AN: 460 Hom.: 177 Cov.: 0 AF XY: 0.880 AC XY: 257 AN XY: 292

Gnomad4 FIN exome AF: 0.868

Gnomad4 NFE exome AF: 0.912

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.721 AC: 109599 AN: 151980 Hom.: 41670 Cov.: 30 AF XY: 0.720 AC XY: 53479 AN XY: 74272

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.752

Alfa AF: 0.814 Hom.: 84025

Bravo AF: 0.706

Asia WGS AF: 0.651 AC: 2263 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

-

- -

Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.0
DANN	Benign	0.76

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: rs12452477; hg19: chr17-48067953;