10-77920676-A-T

Variant names:

• chr10-77920676-A-T
• rs754466
• NM_004747.4:c.304+5541T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004747.4(DLG5):​c.304+5541T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,090 control chromosomes in the GnomAD database, including 3,833 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 0.22 (3833 hom., cov: 32)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 20 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):

• ciliopathy

  Inheritance: AD, AR Classification: LIMITED Submitted by: Franklin by Genoox
• Yuksel-Vogel-Bauer syndrome

  Inheritance: AD, AR Classification: LIMITED Submitted by: G2P
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004747.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	NM_004747.4	MANE Select	c.304+5541T>A		intron	N/A	NP_004738.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	ENST00000372391.7	TSL:1 MANE Select	c.304+5541T>A		intron	N/A	ENSP00000361467.2	Q8TDM6-1
	DLG5	ENST00000928380.1		c.304+5541T>A		intron	N/A	ENSP00000598439.1
	DLG5	ENST00000928379.1		c.304+5541T>A		intron	N/A	ENSP00000598438.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32906 AN: 151972 Hom.: 3835 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.216 AC: 32909 AN: 152090 Hom.: 3833 Cov.: 32 AF XY: 0.215 AC XY: 15945 AN XY: 74330

African (AFR) AF: 0.134 AC: 5542 AN: 41500

American (AMR) AF: 0.196 AC: 3002 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3472

East Asian (EAS) AF: 0.173 AC: 891 AN: 5156

South Asian (SAS) AF: 0.290 AC: 1398 AN: 4818

European-Finnish (FIN) AF: 0.216 AC: 2285 AN: 10566

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17967 AN: 67972

Other (OTH) AF: 0.236 AC: 500 AN: 2116

Alfa AF: 0.253 Hom.: 2716

Bravo AF: 0.211

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.7
DANN	Benign	0.79
PhyloP100		0.55
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: rs754466; hg19: chr10-79680434;