rs1248638

Positions:

• chr10-77816121-A-G

Variant summary

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

The NM_004747.4(DLG5):​c.4025+430T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 478,760 control chromosomes in the GnomAD database, including 117,375 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 0.73 (40816 hom., cov: 33)
  • Exomes 𝑓: 0.68 (76559 hom.)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	NM_004747.4	c.4025+430T>C		intron_variant		ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.4025+430T>C		intron_variant		1	NM_004747.4	ENSP00000361467	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110449 AN: 152024 Hom.: 40767 Cov.: 33

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.709

GnomAD4 exome AF: 0.682 AC: 222782 AN: 326618 Hom.: 76559 Cov.: 0 AF XY: 0.679 AC XY: 125292 AN XY: 184466

Gnomad4 AFR exome AF: 0.848

Gnomad4 AMR exome AF: 0.770

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.739

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.612

Gnomad4 NFE exome AF: 0.664

Gnomad4 OTH exome AF: 0.687

GnomAD4 genome AF: 0.727 AC: 110556 AN: 152142 Hom.: 40816 Cov.: 33 AF XY: 0.723 AC XY: 53791 AN XY: 74368

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.710

Alfa AF: 0.694 Hom.: 4671

Bravo AF: 0.744

Asia WGS AF: 0.765 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.030
DANN	Benign	0.25

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: rs1248638; hg19: chr10-79575879; COSMIC: COSV64948154; COSMIC: COSV64948154;