rs33937843

Variant names:

• chr17-49994861-G-A
• rs33937843
• NM_005220.3:c.138C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-49994861-G-A
• chr17-49994861-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005220.3(DLX3):​c.138C>T​(p.Pro46Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,614,156 control chromosomes in the GnomAD database, including 5,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (929 hom., cov: 34)
  • Exomes 𝑓: 0.059 (4454 hom.)
• Consequence: DLX3 NM_005220.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.174
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-49994861-G-A is Benign according to our data. Variant chr17-49994861-G-A is described in ClinVar as Benign. ClinVar VariationId is 259675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.174 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 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.138C>T	p.Pro46Pro	synonymous	Exon 1 of 3	NP_005211.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX3	ENST00000434704.2	TSL:1 MANE Select	c.138C>T	p.Pro46Pro	synonymous	Exon 1 of 3	ENSP00000389870.2

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13069 AN: 152166 Hom.: 927 Cov.: 34

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0405

Gnomad OTH AF: 0.0632

GnomAD2 exomes AF: 0.0859 AC: 21594 AN: 251386 AF XY: 0.0850

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.0260

Gnomad EAS exome AF: 0.170

Gnomad FIN exome AF: 0.0150

Gnomad NFE exome AF: 0.0390

Gnomad OTH exome AF: 0.0629

GnomAD4 exome AF: 0.0588 AC: 86024 AN: 1461872 Hom.: 4454 Cov.: 32 AF XY: 0.0616 AC XY: 44768 AN XY: 727240

African (AFR) AF: 0.167 AC: 5606 AN: 33480

American (AMR) AF: 0.128 AC: 5747 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 707 AN: 26136

East Asian (EAS) AF: 0.197 AC: 7834 AN: 39700

South Asian (SAS) AF: 0.181 AC: 15582 AN: 86256

European-Finnish (FIN) AF: 0.0181 AC: 964 AN: 53404

Middle Eastern (MID) AF: 0.0560 AC: 323 AN: 5768

European-Non Finnish (NFE) AF: 0.0407 AC: 45251 AN: 1112010

Other (OTH) AF: 0.0664 AC: 4010 AN: 60394

GnomAD4 genome AF: 0.0860 AC: 13098 AN: 152284 Hom.: 929 Cov.: 34 AF XY: 0.0871 AC XY: 6487 AN XY: 74470

African (AFR) AF: 0.164 AC: 6820 AN: 41562

American (AMR) AF: 0.0813 AC: 1244 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3470

East Asian (EAS) AF: 0.179 AC: 926 AN: 5170

South Asian (SAS) AF: 0.194 AC: 935 AN: 4822

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0405 AC: 2752 AN: 68022

Other (OTH) AF: 0.0658 AC: 139 AN: 2112

Alfa AF: 0.0564 Hom.: 692

Bravo AF: 0.0953

Asia WGS AF: 0.205 AC: 715 AN: 3478

EpiCase AF: 0.0391

EpiControl AF: 0.0374

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (2)
-	-	1	not specified (1)
-	-	1	Tricho-dento-osseous syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.94
PhyloP100		0.17
PromoterAI		0.013	Neutral
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: rs33937843; hg19: chr17-48072225; COSMIC: COSV71547533; COSMIC: COSV71547533;