Variant 3-197044683-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001366207.1(DLG1):c.2622A>G(p.Lys874Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 1,605,700 control chromosomes in the GnomAD database, including 2,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.037 ( 165 hom., cov: 32)

Exomes 𝑓: 0.047 ( 1874 hom. )

Consequence

DLG1
NM_001366207.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.510

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 3-197044683-T-C is Benign according to our data. Variant chr3-197044683-T-C is described in ClinVar as [Benign]. Clinvar id is 3057052.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.51 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG1	NM_001366207.1 linkuse as main transcript	c.2622A>G	p.Lys874Lys	synonymous_variant	25/25	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.2622A>G	p.Lys874Lys	synonymous_variant	25/25		NM_001366207.1	ENSP00000499414.1		Q12959-4

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5652

AN:

152192

Hom.:

165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00857

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0501

Gnomad FIN

AF:

0.0774

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0510

Gnomad OTH

AF:

0.0373

GnomAD3 exomes

AF:

0.0421

AC:

10442

AN:

248234

Hom.:

287

AF XY:

0.0441

AC XY:

5927

AN XY:

134336

show subpopulations

Gnomad AFR exome

AF:

0.00719

Gnomad AMR exome

AF:

0.0184

Gnomad ASJ exome

AF:

0.0492

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.0522

Gnomad FIN exome

AF:

0.0739

Gnomad NFE exome

AF:

0.0515

Gnomad OTH exome

AF:

0.0401

GnomAD4 exome

AF:

0.0468

AC:

68091

AN:

1453390

Hom.:

1874

Cov.:

AF XY:

0.0477

AC XY:

34515

AN XY:

723304

show subpopulations

Gnomad4 AFR exome

AF:

0.00707

Gnomad4 AMR exome

AF:

0.0198

Gnomad4 ASJ exome

AF:

0.0480

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0543

Gnomad4 FIN exome

AF:

0.0730

Gnomad4 NFE exome

AF:

0.0492

Gnomad4 OTH exome

AF:

0.0427

GnomAD4 genome

AF:

0.0371

AC:

5654

AN:

152310

Hom.:

165

Cov.:

AF XY:

0.0377

AC XY:

2806

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00854

Gnomad4 AMR

AF:

0.0324

Gnomad4 ASJ

AF:

0.0490

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.0505

Gnomad4 FIN

AF:

0.0774

Gnomad4 NFE

AF:

0.0510

Gnomad4 OTH

AF:

0.0369

Alfa

AF:

0.0418

Hom.:

Bravo

AF:

0.0308

Asia WGS

AF:

0.0240

AC:

AN:

3478

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

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

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.3

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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