Variant 3-197065292-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001366207.1(DLG1):c.2357G>A(p.Arg786Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,606,026 control chromosomes in the GnomAD database, including 402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.015 ( 20 hom., cov: 31)

Exomes 𝑓: 0.021 ( 382 hom. )

Consequence

DLG1
NM_001366207.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.04

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:

DLG1 (HGNC:):

DLG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067587793).

BP6

Variant 3-197065292-C-T is Benign according to our data. Variant chr3-197065292-C-T is described in ClinVar as [Benign]. Clinvar id is 3041899.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0147 (2235/151924) while in subpopulation NFE AF= 0.0238 (1616/67966). AF 95% confidence interval is 0.0228. There are 20 homozygotes in gnomad4. There are 1106 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2235 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG1	NM_001366207.1 linkuse as main transcript	c.2357G>A	p.Arg786Gln	missense_variant	22/25	ENST00000667157.1	NP_001353136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG1	ENST00000667157.1 linkuse as main transcript	c.2357G>A	p.Arg786Gln	missense_variant	22/25		NM_001366207.1	ENSP00000499414.1		Q12959-4

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2235

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00389

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00526

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00748

Gnomad FIN

AF:

0.0291

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.00912

GnomAD3 exomes

AF:

0.0165

AC:

4032

AN:

244010

Hom.:

AF XY:

0.0168

AC XY:

2215

AN XY:

131934

show subpopulations

Gnomad AFR exome

AF:

0.00341

Gnomad AMR exome

AF:

0.00527

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.00727

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.0251

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0207

AC:

30160

AN:

1454102

Hom.:

382

Cov.:

AF XY:

0.0205

AC XY:

14830

AN XY:

723296

show subpopulations

Gnomad4 AFR exome

AF:

0.00275

Gnomad4 AMR exome

AF:

0.00571

Gnomad4 ASJ exome

AF:

0.00570

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00755

Gnomad4 FIN exome

AF:

0.0290

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0180

GnomAD4 genome

AF:

0.0147

AC:

2235

AN:

151924

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1106

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.00388

Gnomad4 AMR

AF:

0.00525

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00749

Gnomad4 FIN

AF:

0.0291

Gnomad4 NFE

AF:

0.0238

Gnomad4 OTH

AF:

0.00902

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0124

TwinsUK

AF:

0.0218

AC:

ALSPAC

AF:

0.0200

AC:

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.0245

AC:

211

ExAC

AF:

0.0170

AC:

2061

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DLG1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 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

0.16

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

.;T;T;.;.;T;.;.;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.99

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

MetaRNN

Benign

0.0068

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;.;L;.;.;L;.;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.1

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

REVEL

Benign

0.11

Sift

Benign

0.10

T;.;T;T;T;T;T;D;T

Sift4G

Benign

0.21

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

Polyphen

0.99

D;.;P;.;.;P;.;P;.

Vest4

0.57

MPC

0.74

ClinPred

0.039

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.87

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