NM_005220.3:c.*1168delA

Variant names:

• chr17-49990348-CT-C
• rs61087392
• NM_005220.3:c.*1168delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005220.3(DLX3):​c.*1168delA 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
• Publications: 1 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 -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 VariationId 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.

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.*1168delA		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.*1168delA		3_prime_UTR	Exon 3 of 3	ENSP00000389870.2	O60479

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0952 AC: 4 AN: 42

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00103286), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0992 AC: 3764 AN: 37932

American (AMR) AF: 0.0529 AC: 733 AN: 13868

Ashkenazi Jewish (ASJ) AF: 0.0367 AC: 122 AN: 3324

East Asian (EAS) AF: 0.00578 AC: 28 AN: 4846

South Asian (SAS) AF: 0.0921 AC: 399 AN: 4334

European-Finnish (FIN) AF: 0.0564 AC: 421 AN: 7468

Middle Eastern (MID) AF: 0.0730 AC: 20 AN: 274

European-Non Finnish (NFE) AF: 0.0907 AC: 5857 AN: 64546

Other (OTH) AF: 0.0660 AC: 129 AN: 1956

Alfa AF: 0.0188 Hom.: 25

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Amelogenesis Imperfecta, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=99/1	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: rs61087392; hg19: chr17-48067712;