rs797045525

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_021120.4(DLG3):c.1405+5_1405+7delGAG variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000303 in 1,197,885 control chromosomes in the GnomAD database, including 2 homozygotes. There are 95 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., 45 hem., cov: 23)

Exomes 𝑓: 0.00018 ( 0 hom. 50 hem. )

Consequence

DLG3
NM_021120.4 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 5.18

Publications

0 publications found

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:40182): (DLG3 antisense RNA 1)

DLG3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant X-70454318-TAGG-T is Benign according to our data. Variant chrX-70454318-TAGG-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210850.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG3	NM_021120.4 link	c.1405+5_1405+7delGAG		splice_region_variant, intron_variant	Intron 9 of 18	ENST00000374360.8	NP_066943.2	Q92796-1Q59FY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG3	ENST00000374360.8 link	c.1405+3_1405+5delAGG		splice_region_variant, intron_variant	Intron 9 of 18	1	NM_021120.4	ENSP00000363480.3		Q92796-1

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

172

AN:

111637

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00541

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.000661

GnomAD2 exomes

AF:

0.000504

AC:

AN:

180568

AF XY:

0.000292

show subpopulations

Gnomad AFR exome

AF:

0.00632

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000634

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000176

AC:

191

AN:

1086193

Hom.:

AF XY:

0.000142

AC XY:

AN XY:

351899

show subpopulations

African (AFR)

AF:

0.00623

AC:

163

AN:

26175

American (AMR)

AF:

0.000171

AC:

AN:

35128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19301

East Asian (EAS)

AF:

0.00

AC:

AN:

30153

South Asian (SAS)

AF:

0.00

AC:

AN:

53571

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40494

Middle Eastern (MID)

AF:

0.000487

AC:

AN:

4103

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

831568

Other (OTH)

AF:

0.000350

AC:

AN:

45700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00154

AC:

172

AN:

111692

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

33912

show subpopulations

African (AFR)

AF:

0.00539

AC:

166

AN:

30781

American (AMR)

AF:

0.000378

AC:

AN:

10579

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00

AC:

AN:

3523

South Asian (SAS)

AF:

0.00

AC:

AN:

2616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6081

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

53031

Other (OTH)

AF:

0.000652

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.00186

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 03, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Uncertain:1

May 01, 2014

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 01, 2018

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

DLG3-related disorder

Benign:1

Jan 28, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.2

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.33

Position offset: 13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over