rs1248653

Positions:

• chr10-77866771-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004747.4(DLG5):​c.373+2358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 353,608 control chromosomes in the GnomAD database, including 14,230 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 0.25 (5473 hom., cov: 30)
  • Exomes 𝑓: 0.29 (8757 hom.)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	NM_004747.4	c.373+2358A>G		intron_variant		ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.373+2358A>G		intron_variant		1	NM_004747.4	ENSP00000361467.2
DLG5	ENST00000468332.6	n.148+2358A>G		intron_variant		2		ENSP00000473298.1
DLG5	ENST00000475613.6	n.93+2328A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38507 AN: 151374 Hom.: 5465 Cov.: 30

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.288 AC: 58197 AN: 202114 Hom.: 8757 AF XY: 0.289 AC XY: 32177 AN XY: 111180

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.435

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.254 AC: 38521 AN: 151494 Hom.: 5473 Cov.: 30 AF XY: 0.259 AC XY: 19189 AN XY: 73996

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.235

Alfa AF: 0.259 Hom.: 872

Bravo AF: 0.254

Asia WGS AF: 0.320 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1248653; hg19: chr10-79626529; COSMIC: COSV64946441; COSMIC: COSV64946441;