Variant chr17-7217159-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001321075.3(DLG4):c.-12A>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000652 in 1,288,510 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00065 ( 1 hom. )

Consequence

DLG4
NM_001321075.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.76

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:

ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACADVL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21365088).

BP6

Variant 17-7217159-T-C is Benign according to our data. Variant chr17-7217159-T-C is described in ClinVar as [Benign]. Clinvar id is 1176656.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 96 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG4	NM_001321075.3 linkuse as main transcript	c.-12A>G		5_prime_UTR_variant	1/20	ENST00000399506.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG4	ENST00000399506.9 linkuse as main transcript	c.-12A>G		5_prime_UTR_variant	1/20	2	NM_001321075.3	A1	P78352-1

Frequencies

GnomAD3 genomes

AF:

0.000633

AC:

AN:

151668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000833

Gnomad FIN

AF:

0.00218

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000781

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00129

AC:

AN:

26390

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

12258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00215

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.000655

AC:

744

AN:

1136728

Hom.:

Cov.:

AF XY:

0.000609

AC XY:

332

AN XY:

544790

show subpopulations

Gnomad4 AFR exome

AF:

0.000128

Gnomad4 AMR exome

AF:

0.000106

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.00147

Gnomad4 NFE exome

AF:

0.000686

Gnomad4 OTH exome

AF:

0.000505

GnomAD4 genome

AF:

0.000632

AC:

AN:

151782

Hom.:

Cov.:

AF XY:

0.000687

AC XY:

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000833

Gnomad4 FIN

AF:

0.00218

Gnomad4 NFE

AF:

0.000781

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000529

Hom.:

Bravo

AF:

0.000487

ExAC

AF:

0.000340

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

DLG4: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.90

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.28

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.21

MetaSVM

Pathogenic

0.98

MutationTaster

Benign

0.91

D;D;D;D;D;D

PROVEAN

Benign

-0.24

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Vest4

0.58

MVP

0.91

MPC

0.89

ClinPred

0.18

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

gMVP

0.69

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