chr17-49992861-C-T

Variant names:

• chr17-49992861-C-T
• rs3891034
• NM_005220.3:c.516+539G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005220.3(DLX3):​c.516+539G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,064 control chromosomes in the GnomAD database, including 3,039 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3039 hom., cov: 32)
• Consequence: DLX3 NM_005220.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX3	NM_005220.3	c.516+539G>A		intron_variant	Intron 2 of 2	ENST00000434704.2	NP_005211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX3	ENST00000434704.2	c.516+539G>A		intron_variant	Intron 2 of 2	1	NM_005220.3	ENSP00000389870.2
DLX3	ENST00000512495.2	c.156+539G>A		intron_variant	Intron 1 of 1	2		ENSP00000449976.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28392 AN: 151946 Hom.: 3040 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.187 AC: 28397 AN: 152064 Hom.: 3039 Cov.: 32 AF XY: 0.191 AC XY: 14221 AN XY: 74326

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.185

Alfa AF: 0.186 Hom.: 4431

Bravo AF: 0.179

Asia WGS AF: 0.311 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.9
DANN	Benign	0.53

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: rs3891034; hg19: chr17-48070225;