Genetic Variant NM_004747.4:c.4968-36C>T (chr10-77805897-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004747.4(DLG5):c.4968-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,575,354 control chromosomes in the GnomAD database, including 85,586 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 ( 7276 hom., cov: 32)

Exomes 𝑓: 0.33 ( 78310 hom. )

Consequence

DLG5
NM_004747.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.487

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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 rank	MANE	Protein	UniProt
DLG5	NM_004747.4 link	c.4968-36C>T		intron_variant	Intron 26 of 31	ENST00000372391.7	NP_004738.3	Q8TDM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7 link	c.4968-36C>T		intron_variant	Intron 26 of 31	1	NM_004747.4	ENSP00000361467.2		Q8TDM6-1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46267

AN:

151972

Hom.:

7276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.302

AC:

69735

AN:

231068

Hom.:

10924

AF XY:

0.306

AC XY:

38085

AN XY:

124444

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.329

AC:

468533

AN:

1423264

Hom.:

78310

Cov.:

AF XY:

0.328

AC XY:

230781

AN XY:

702916

show subpopulations

Gnomad4 AFR exome

AF:

0.271

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.360

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:

46269

AN:

152090

Hom.:

7276

Cov.:

AF XY:

0.301

AC XY:

22385

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.270

Gnomad4 ASJ

AF:

0.359

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.348

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.248

Hom.:

1077

Bravo

AF:

0.303

Asia WGS

AF:

0.255

AC:

890

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.5

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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