rs565495109

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000648172.9(DLG4):c.94A>G(p.Ser32Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000253 in 1,564,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

DLG4
ENST00000648172.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.10

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

very long chain acyl-CoA dehydrogenase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACADVL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007270336).

BP6

Variant 17-7218565-T-C is Benign according to our data. Variant chr17-7218565-T-C is described in ClinVar as [Benign]. Clinvar id is 2647321.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
DLG4	NM_001365.5 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 2 of 22	NP_001356.1	P78352-2B7Z647B9EGL1
DLG4	NM_001321074.1 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 2 of 22	NP_001308003.1	B9EGL1
DLG4	NR_135527.1 link	n.1295A>G		non_coding_transcript_exon_variant	Exon 2 of 21
ACADVL	NM_001270447.2 link	c.131+747T>C		intron_variant	Intron 2 of 20	NP_001257376.1	P49748-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
DLG4	ENST00000648172.9 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 2 of 22		ENSP00000497806.3	P78352-2
DLG4	ENST00000399510.8 link	c.94A>G	p.Ser32Gly	missense_variant	Exon 2 of 22	1	ENSP00000382428.3	B9EGL1
DLG4	ENST00000491753.2 link	n.94A>G		non_coding_transcript_exon_variant	Exon 2 of 21	2	ENSP00000467897.2	B7Z3U2
ACADVL	ENST00000543245.6 link	c.131+747T>C		intron_variant	Intron 2 of 20	2	ENSP00000438689.2	P49748-3

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000649

AC:

112

AN:

172638

AF XY:

0.000846

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000280

Gnomad OTH exome

AF:

0.000213

GnomAD4 exome

AF:

0.000268

AC:

378

AN:

1411842

Hom.:

Cov.:

AF XY:

0.000371

AC XY:

259

AN XY:

697582

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32174

American (AMR)

AF:

0.00

AC:

AN:

37056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25300

East Asian (EAS)

AF:

0.00

AC:

AN:

36786

South Asian (SAS)

AF:

0.00411

AC:

329

AN:

79972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50078

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000249

AC:

AN:

1086210

Other (OTH)

AF:

0.000359

AC:

AN:

58552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

118

147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000118

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41530

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00352

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000321

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000382

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DLG4-related disorder

Benign:1

Feb 17, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DLG4: PP2, BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

.;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.0022

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-1.0

PhyloP100

4.1

PROVEAN

Benign

-0.65

.;N

REVEL

Benign

0.048

Sift

Uncertain

0.0090

.;D

Sift4G

Benign

0.088

.;T

Polyphen

0.22

B;B

Vest4

0.53

MutPred

0.60

Gain of catalytic residue at S32 (P = 0.0244);Gain of catalytic residue at S32 (P = 0.0244);

MVP

0.62

MPC

1.1

ClinPred

0.046

GERP RS

4.5

gMVP

0.37

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs565495109

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over