17-49990292-TA-T

Position:

• chr17-49990292-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005220.3(DLX3):​c.*1224del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 140,764 control chromosomes in the GnomAD database, including 737 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (737 hom., cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLX3 NM_005220.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

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 -10 ACMG points.

• BP6: Variant 17-49990292-TA-T is Benign according to our data. Variant chr17-49990292-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 324006.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX3	NM_005220.3	c.*1224del		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.*1224del		3_prime_UTR_variant	3/3	1	NM_005220.3	ENSP00000389870	P1

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 10419 AN: 140734 Hom.: 739 Cov.: 28

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0878

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.0741

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0740 AC: 10410 AN: 140764 Hom.: 737 Cov.: 28 AF XY: 0.0771 AC XY: 5245 AN XY: 67990

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.0985

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0758

Gnomad4 OTH AF: 0.0756

Bravo AF: 0.0672

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Amelogenesis Imperfecta, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3840066; hg19: chr17-48067656;