rs12452477

Variant names:

• chr17-49990589-T-C
• rs12452477
• NM_005220.3:c.*928A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-49990589-T-C
• chr17-49990589-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

DLX3 Gene-Disease associations (from GenCC):

• tricho-dento-osseous syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005220.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX3	NM_005220.3	MANE Select	c.*928A>G		3_prime_UTR	Exon 3 of 3	NP_005211.1	O60479

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX3	ENST00000434704.2	TSL:1 MANE Select	c.*928A>G		3_prime_UTR	Exon 3 of 3	ENSP00000389870.2	O60479

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.868 AC: 354 AN: 408

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.912 AC: 31 AN: 34

Other (OTH) AF: 1.00 AC: 16 AN: 16

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

African (AFR) AF: 0.468 AC: 19375 AN: 41410

American (AMR) AF: 0.791 AC: 12082 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2726 AN: 3470

East Asian (EAS) AF: 0.713 AC: 3671 AN: 5150

South Asian (SAS) AF: 0.663 AC: 3184 AN: 4806

European-Finnish (FIN) AF: 0.848 AC: 8972 AN: 10578

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56996 AN: 67980

Other (OTH) AF: 0.752 AC: 1588 AN: 2112

Alfa AF: 0.798 Hom.: 186172

Bravo AF: 0.706

Asia WGS AF: 0.651 AC: 2263 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.0
DANN	Benign	0.76
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12452477; hg19: chr17-48067953;