rs1248623

Variant names:

• chr10-77813755-T-C
• rs1248623
• NM_004747.4:c.4026-1378A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• Yuksel-Vogel-Bauer syndrome

  Inheritance: AD, AR Classification: LIMITED Submitted by: G2P
• ciliopathy

  Inheritance: AR, AD Classification: LIMITED Submitted by: Franklin by Genoox
• congenital anomaly of kidney and urinary tract

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.4026-1378A>G		intron_variant	Intron 20 of 31	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.4026-1378A>G		intron_variant	Intron 20 of 31	1	NM_004747.4	ENSP00000361467.2

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

African (AFR) AF: 0.784 AC: 32554 AN: 41512

American (AMR) AF: 0.747 AC: 11413 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2380 AN: 3472

East Asian (EAS) AF: 0.739 AC: 3810 AN: 5158

South Asian (SAS) AF: 0.678 AC: 3259 AN: 4806

European-Finnish (FIN) AF: 0.611 AC: 6449 AN: 10558

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45128 AN: 67974

Other (OTH) AF: 0.695 AC: 1467 AN: 2112

Alfa AF: 0.699 Hom.: 6145

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
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1248623; hg19: chr10-79573513;