Variant chrX-70453614-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021120.4(DLG3):c.1146-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,202,579 control chromosomes in the GnomAD database, including 14,093 homozygotes. There are 68,994 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1103 hom., 4792 hem., cov: 22)

Exomes 𝑓: 0.18 ( 12990 hom. 64202 hem. )

Consequence

DLG3
NM_021120.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.286

Variant links:

Genes affected

DLG3 (HGNC:2902): (discs large MAGUK scaffold protein 3) This gene encodes a member of the membrane-associated guanylate kinase protein family. The encoded protein may play a role in clustering of NMDA receptors at excitatory synapses. It may also negatively regulate cell proliferation through interaction with the C-terminal region of the adenomatosis polyposis coli tumor suppressor protein. Mutations in this gene have been associated with X-linked cognitive disability. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

DLG3 links:

DLG3-AS1 (HGNC:):

DLG3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-70453614-C-T is Benign according to our data. Variant chrX-70453614-C-T is described in ClinVar as [Benign]. Clinvar id is 1225363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG3	NM_021120.4 linkuse as main transcript	c.1146-23C>T		intron_variant		ENST00000374360.8	NP_066943.2	Q92796-1Q59FY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG3	ENST00000374360.8 linkuse as main transcript	c.1146-23C>T		intron_variant		1	NM_021120.4	ENSP00000363480.3		Q92796-1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

16671

AN:

111031

Hom.:

1108

Cov.:

AF XY:

0.144

AC XY:

4787

AN XY:

33233

show subpopulations

Gnomad AFR

AF:

0.0839

Gnomad AMI

AF:

0.165

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.00759

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.208

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.146

AC:

24680

AN:

169224

Hom.:

1556

AF XY:

0.143

AC XY:

8001

AN XY:

55776

show subpopulations

Gnomad AFR exome

AF:

0.0819

Gnomad AMR exome

AF:

0.0688

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.00509

Gnomad SAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.278

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.181

AC:

197024

AN:

1091494

Hom.:

12990

Cov.:

AF XY:

0.179

AC XY:

64202

AN XY:

358246

show subpopulations

Gnomad4 AFR exome

AF:

0.0815

Gnomad4 AMR exome

AF:

0.0739

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.00366

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.150

AC:

16668

AN:

111085

Hom.:

1103

Cov.:

AF XY:

0.144

AC XY:

4792

AN XY:

33297

show subpopulations

Gnomad4 AFR

AF:

0.0838

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.00761

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.169

Hom.:

1449

Bravo

AF:

0.138

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.3

DANN

Benign

0.65

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