Variant rs1248634 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004747.4(DLG5):c.3528C>T(p.Gly1176Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,612,028 control chromosomes in the GnomAD database, including 66,437 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5320 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61117 hom. )

Consequence

DLG5
NM_004747.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0003867

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.319

Variant links:

Genes affected

DLG5 (HGNC:2904): (discs large MAGUK scaffold protein 5) This gene encodes a member of the family of discs large (DLG) homologs, a subset of the membrane-associated guanylate kinase (MAGUK) superfamily. The MAGUK proteins are composed of a catalytically inactive guanylate kinase domain, in addition to PDZ and SH3 domains, and are thought to function as scaffolding molecules at sites of cell-cell contact. The protein encoded by this gene localizes to the plasma membrane and cytoplasm, and interacts with components of adherens junctions and the cytoskeleton. It is proposed to function in the transmission of extracellular signals to the cytoskeleton and in the maintenance of epithelial cell structure. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

DLG5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=0.319 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	NM_004747.4 link	c.3528C>T	p.Gly1176Gly	splice_region_variant, synonymous_variant	17/32	ENST00000372391.7	NP_004738.3	Q8TDM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7 link	c.3528C>T	p.Gly1176Gly	splice_region_variant, synonymous_variant	17/32	1	NM_004747.4	ENSP00000361467.2		Q8TDM6-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37623

AN:

151934

Hom.:

5313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.293

AC:

73059

AN:

248956

Hom.:

11695

AF XY:

0.290

AC XY:

39085

AN XY:

134592

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.291

Gnomad SAS exome

AF:

0.308

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.285

AC:

416779

AN:

1459978

Hom.:

61117

Cov.:

AF XY:

0.284

AC XY:

206448

AN XY:

726274

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.316

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.294

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.248

AC:

37642

AN:

152050

Hom.:

5320

Cov.:

AF XY:

0.253

AC XY:

18783

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.383

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.300

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.276

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.268

Hom.:

9113

Bravo

AF:

0.247

Asia WGS

AF:

0.309

AC:

1078

AN:

3478

EpiCase

AF:

0.259

EpiControl

AF:

0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over