chr17-49990348-CT-C

Position:

• chr17-49990348-CT-C

Variant summary

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

The NM_005220.3(DLX3):​c.*1168del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 139,470 control chromosomes in the GnomAD database, including 489 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.083 (489 hom., cov: 22)
  • Exomes 𝑓: 0.095 (0 hom.)
• Consequence: DLX3 NM_005220.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.106

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 17-49990348-CT-C is Benign according to our data. Variant chr17-49990348-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 324008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLX3	NM_005220.3	c.*1168del		3_prime_UTR_variant	3/3	ENST00000434704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLX3	ENST00000434704.2	c.*1168del		3_prime_UTR_variant	3/3	1	NM_005220.3	P1

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 11561 AN: 139420 Hom.: 489 Cov.: 22

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.0955

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.0367

Gnomad EAS AF: 0.00576

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.0664

GnomAD4 exome AF: 0.0952 AC: 4 AN: 42 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 2 AN XY: 28

Gnomad4 FIN exome AF: 0.0952

GnomAD4 genome AF: 0.0829 AC: 11557 AN: 139428 Hom.: 489 Cov.: 22 AF XY: 0.0800 AC XY: 5370 AN XY: 67120

Gnomad4 AFR AF: 0.0992

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0367

Gnomad4 EAS AF: 0.00578

Gnomad4 SAS AF: 0.0921

Gnomad4 FIN AF: 0.0564

Gnomad4 NFE AF: 0.0907

Gnomad4 OTH AF: 0.0660

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: rs61087392; hg19: chr17-48067712;