Variant 10-77806874-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004747.4(DLG5):c.4851C>T(p.Asp1617Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,613,428 control chromosomes in the GnomAD database, including 87,643 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7271 hom., cov: 32)

Exomes 𝑓: 0.33 ( 80372 hom. )

Consequence

DLG5
NM_004747.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

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:

DLG5 (HGNC:):

DLG5 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 (BayesDel_noAF=-0.76).

BP7

Synonymous conserved (PhyloP=-1.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	NM_004747.4 linkuse as main transcript	c.4851C>T	p.Asp1617Asp	synonymous_variant	26/32	ENST00000372391.7	NP_004738.3	Q8TDM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7 linkuse as main transcript	c.4851C>T	p.Asp1617Asp	synonymous_variant	26/32	1	NM_004747.4	ENSP00000361467.2		Q8TDM6-1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46250

AN:

151906

Hom.:

7271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.300

AC:

75456

AN:

251426

Hom.:

11842

AF XY:

0.304

AC XY:

41285

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.278

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.329

AC:

480910

AN:

1461404

Hom.:

80372

Cov.:

AF XY:

0.328

AC XY:

238719

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.361

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.345

Gnomad4 OTH exome

AF:

0.317

GnomAD4 genome

AF:

0.304

AC:

46252

AN:

152024

Hom.:

7271

Cov.:

AF XY:

0.301

AC XY:

22360

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.259

Gnomad4 NFE

AF:

0.348

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.341

Hom.:

11718

Bravo

AF:

0.303

Asia WGS

AF:

0.255

AC:

890

AN:

3478

EpiCase

AF:

0.362

EpiControl

AF:

0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.019

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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