rs17203281

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001321075.3(DLG4):c.1167C>T(p.Ile389Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,368 control chromosomes in the GnomAD database, including 77,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6382 hom., cov: 32)

Exomes 𝑓: 0.31 ( 70993 hom. )

Consequence

DLG4
NM_001321075.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.74

Variant links:

Genes affected

DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DLG4 links:

DLG4 (HGNC:):

DLG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 17-7196492-G-A is Benign according to our data. Variant chr17-7196492-G-A is described in ClinVar as [Benign]. Clinvar id is 1255506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG4	NM_001321075.3 linkuse as main transcript	c.1167C>T	p.Ile389Ile	synonymous_variant	10/20	ENST00000399506.9	NP_001308004.1	P78352-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DLG4	ENST00000399506.9 linkuse as main transcript	c.1167C>T	p.Ile389Ile	synonymous_variant	10/20	2	NM_001321075.3	ENSP00000382425.2	P78352-1
DLG4	ENST00000648172.8 linkuse as main transcript	c.1296C>T	p.Ile432Ile	synonymous_variant	12/22			ENSP00000497806.3	P78352-2
DLG4	ENST00000648896.1 linkuse as main transcript	c.1266C>T	p.Ile422Ile	synonymous_variant	10/20			ENSP00000497546.1	A0A3B3ISQ5
DLG4	ENST00000649520.1 linkuse as main transcript	c.987C>T	p.Ile329Ile	synonymous_variant	9/19			ENSP00000497647.1	B7Z647
DLG4	ENST00000648263.1 linkuse as main transcript	c.987C>T	p.Ile329Ile	synonymous_variant	8/14			ENSP00000498035.1	A0A3B3IU19
DLG4	ENST00000491753.2 linkuse as main transcript	n.1296C>T		non_coding_transcript_exon_variant	12/21	2		ENSP00000467897.2	B7Z3U2

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42701

AN:

151992

Hom.:

6380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.300

GnomAD3 exomes

AF:

0.283

AC:

70531

AN:

249188

Hom.:

10847

AF XY:

0.286

AC XY:

38690

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.307

Gnomad EAS exome

AF:

0.312

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.402

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.307

AC:

449018

AN:

1461258

Hom.:

70993

Cov.:

AF XY:

0.306

AC XY:

222099

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.394

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.281

AC:

42707

AN:

152110

Hom.:

6382

Cov.:

AF XY:

0.281

AC XY:

20898

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.310

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.394

Gnomad4 NFE

AF:

0.326

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.310

Hom.:

12413

Bravo

AF:

0.264

Asia WGS

AF:

0.211

AC:

735

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Jul 03, 2018	- -

Intellectual developmental disorder 62

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

DLG4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

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

BayesDel_noAF

Benign

-0.31

CADD

Benign

9.3

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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