rs1268514

Variant names:

• chr10-77818534-A-C
• rs1268514
• NM_004747.4:c.3672-645T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-77818534-A-C
• chr10-77818534-A-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.3672-645T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,146 control chromosomes in the GnomAD database, including 40,882 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 (40882 hom., cov: 33)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.3672-645T>G		intron_variant	Intron 17 of 31	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.3672-645T>G		intron_variant	Intron 17 of 31	1	NM_004747.4	ENSP00000361467.2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110552 AN: 152028 Hom.: 40839 Cov.: 33

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.727 AC: 110649 AN: 152146 Hom.: 40882 Cov.: 33 AF XY: 0.724 AC XY: 53846 AN XY: 74368

African (AFR) AF: 0.858 AC: 35627 AN: 41538

American (AMR) AF: 0.756 AC: 11558 AN: 15294

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

East Asian (EAS) AF: 0.736 AC: 3790 AN: 5148

South Asian (SAS) AF: 0.678 AC: 3269 AN: 4822

European-Finnish (FIN) AF: 0.611 AC: 6465 AN: 10574

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

European-Non Finnish (NFE) AF: 0.664 AC: 45139 AN: 67984

Other (OTH) AF: 0.705 AC: 1489 AN: 2112

Alfa AF: 0.687 Hom.: 47475

Bravo AF: 0.745

Asia WGS AF: 0.751 AC: 2611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.85
PhyloP100		-0.85
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: rs1268514; hg19: chr10-79578292;