rs1058198

chr10-77806874-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004747.4(DLG5):c.4851C>T(p.Asp1617=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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]

ACMG classification

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	UniProt
DLG5	NM_004747.4	c.4851C>T	p.Asp1617=	synonymous_variant	26/32	ENST00000372391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG5	ENST00000372391.7	c.4851C>T	p.Asp1617=	synonymous_variant	26/32	1	NM_004747.4	P1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46250 AN: 151906 Hom.: 7271 Cov.: 32

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

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.: 55 AF XY: 0.328 AC XY: 238719 AN XY: 726932

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.: 32 AF XY: 0.301 AC XY: 22360 AN XY: 74298

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

Other links and lift over

dbSNP: rs1058198; hg19: chr10-79566632; COSMIC: COSV64947660;