Variant 3-197044642-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001366207.1(DLG1):c.2663C>T(p.Pro888Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0454 in 1,600,904 control chromosomes in the GnomAD database, including 1,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.037 ( 164 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1829 hom. )

Consequence

DLG1
NM_001366207.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.86

Variant links:

Genes affected

DLG1 (HGNC:2900): (discs large MAGUK scaffold protein 1) This gene encodes a multi-domain scaffolding protein that is required for normal development. This protein may have a role in septate junction formation, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. A multitude of transcript variants deriving from alternative splicing and the use of multiple alternate promoter have been observed, including some splice variants that may be specific to brain and other tissues. An upstream uORF may regulate translation at some splice variants of this gene. [provided by RefSeq, Sep 2018]

DLG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050454736).

BP6

Variant 3-197044642-G-A is Benign according to our data. Variant chr3-197044642-G-A is described in ClinVar as [Benign]. Clinvar id is 3056864.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG1	NM_001366207.1 linkuse as main transcript	c.2663C>T	p.Pro888Leu	missense_variant	25/25	ENST00000667157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG1	ENST00000667157.1 linkuse as main transcript	c.2663C>T	p.Pro888Leu	missense_variant	25/25		NM_001366207.1		Q12959-4

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5646

AN:

152112

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00855

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0323

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0503

Gnomad FIN

AF:

0.0774

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0509

Gnomad OTH

AF:

0.0374

GnomAD3 exomes

AF:

0.0415

AC:

10167

AN:

245198

Hom.:

273

AF XY:

0.0434

AC XY:

5751

AN XY:

132548

show subpopulations

Gnomad AFR exome

AF:

0.00690

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0489

Gnomad EAS exome

AF:

0.000835

Gnomad SAS exome

AF:

0.0505

Gnomad FIN exome

AF:

0.0736

Gnomad NFE exome

AF:

0.0508

Gnomad OTH exome

AF:

0.0397

GnomAD4 exome

AF:

0.0463

AC:

67049

AN:

1448674

Hom.:

1829

Cov.:

AF XY:

0.0471

AC XY:

33961

AN XY:

720808

show subpopulations

Gnomad4 AFR exome

AF:

0.00684

Gnomad4 AMR exome

AF:

0.0194

Gnomad4 ASJ exome

AF:

0.0478

Gnomad4 EAS exome

AF:

0.000457

Gnomad4 SAS exome

AF:

0.0534

Gnomad4 FIN exome

AF:

0.0732

Gnomad4 NFE exome

AF:

0.0486

Gnomad4 OTH exome

AF:

0.0421

GnomAD4 genome

AF:

0.0371

AC:

5648

AN:

152230

Hom.:

164

Cov.:

AF XY:

0.0376

AC XY:

2801

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00852

Gnomad4 AMR

AF:

0.0322

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0508

Gnomad4 FIN

AF:

0.0774

Gnomad4 NFE

AF:

0.0509

Gnomad4 OTH

AF:

0.0370

Alfa

AF:

0.0464

Hom.:

300

Bravo

AF:

0.0308

TwinsUK

AF:

0.0448

AC:

166

ALSPAC

AF:

0.0490

AC:

189

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.0471

AC:

405

ExAC

AF:

0.0435

AC:

5276

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DLG1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.29

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;.;D;D;D;D;D;D

MetaRNN

Benign

0.0050

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.73

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-9.1

D;.;D;D;D;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0050

D;.;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;.;.;D;.;D;.

Vest4

0.35

MPC

0.34

ClinPred

0.042

GERP RS

5.5

Varity_R

0.82

gMVP

0.73

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