rs1248638

Variant names:

• chr10-77816121-A-G
• rs1248638
• NM_004747.4:c.4025+430T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.96).
• 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 rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.4025+430T>C		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.4025+430T>C		intron_variant	Intron 20 of 31	1	NM_004747.4	ENSP00000361467.2

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

African (AFR) AF: 0.848 AC: 8195 AN: 9660

American (AMR) AF: 0.770 AC: 21455 AN: 27846

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 8021 AN: 11724

East Asian (EAS) AF: 0.739 AC: 7635 AN: 10338

South Asian (SAS) AF: 0.673 AC: 40354 AN: 59936

European-Finnish (FIN) AF: 0.612 AC: 8622 AN: 14082

Middle Eastern (MID) AF: 0.644 AC: 1867 AN: 2900

European-Non Finnish (NFE) AF: 0.664 AC: 115760 AN: 174312

Other (OTH) AF: 0.687 AC: 10873 AN: 15820

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

African (AFR) AF: 0.855 AC: 35523 AN: 41532

American (AMR) AF: 0.756 AC: 11561 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2381 AN: 3470

East Asian (EAS) AF: 0.740 AC: 3814 AN: 5152

South Asian (SAS) AF: 0.678 AC: 3267 AN: 4820

European-Finnish (FIN) AF: 0.610 AC: 6452 AN: 10570

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45128 AN: 67992

Other (OTH) AF: 0.710 AC: 1499 AN: 2112

Alfa AF: 0.701 Hom.: 4959

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
PhyloP100		-1.4
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: rs1248638; hg19: chr10-79575879; COSMIC: COSV64948154; COSMIC: COSV64948154;