rs1248623

Positions:

• chr10-77813755-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.4026-1378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,086 control chromosomes in the GnomAD database, including 38,232 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 0.71 (38232 hom., cov: 32)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG5	NM_004747.4	c.4026-1378A>G		intron_variant		ENST00000372391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG5	ENST00000372391.7	c.4026-1378A>G		intron_variant		1	NM_004747.4	P1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107297 AN: 151968 Hom.: 38195 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.706 AC: 107387 AN: 152086 Hom.: 38232 Cov.: 32 AF XY: 0.705 AC XY: 52367 AN XY: 74326

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.695

Alfa AF: 0.696 Hom.: 5897

Bravo AF: 0.721

Asia WGS AF: 0.747 AC: 2599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.16
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1248623; hg19: chr10-79573513;