Variant chr17-49969536-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138281.3(DLX4):c.68C>G(p.Pro23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DLX4
NM_138281.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

DLX4 (HGNC:2917): (distal-less homeobox 4) 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. The DLX proteins are postulated to play a role in forebrain and craniofacial development. Three transcript variants have been described for this gene, however, the full length nature of one variant has not been described. Studies of the two splice variants revealed that one encoded isoform functions as a repressor of the beta-globin gene while the other isoform lacks that function. [provided by RefSeq, Jul 2008]

DLX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX4	NM_138281.3 link	c.68C>G	p.Pro23Arg	missense_variant	1/3	ENST00000240306.5	NP_612138.1	Q92988-1
DLX4	XM_047435517.1 link	c.-3391-79C>G		intron_variant			XP_047291473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DLX4	ENST00000240306.5 link	c.68C>G	p.Pro23Arg	missense_variant	1/3	1	NM_138281.3	ENSP00000240306.3	Q92988-1
DLX4	ENST00000505318.2 link	n.207C>G		non_coding_transcript_exon_variant	1/2	3
DLX4	ENST00000706528.1 link	n.949C>G		non_coding_transcript_exon_variant	1/3
DLX4	ENST00000503410.1 link	n.71-79C>G		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.68C>G (p.P23R) alteration is located in exon 1 (coding exon 1) of the DLX4 gene. This alteration results from a C to G substitution at nucleotide position 68, causing the proline (P) at amino acid position 23 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

Eigen

Benign

0.14

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.28

MetaRNN

Uncertain

0.49

MetaSVM

Uncertain

0.098

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.41

Sift

Benign

0.048

Sift4G

Benign

0.19

Polyphen

0.99

Vest4

0.37

MutPred

0.34

Gain of solvent accessibility (P = 0.0411);

MVP

0.95

MPC

0.85

ClinPred

0.78

GERP RS

3.0

Varity_R

0.096

gMVP

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over