10-77818468-C-G

Variant names:

• chr10-77818468-C-G
• rs1270911
• NM_004747.4:c.3672-579G>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.3672-579G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,174 control chromosomes in the GnomAD database, including 5,330 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 0.25 (5330 hom., cov: 32)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.376 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.3672-579G>C		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.3672-579G>C		intron	N/A	ENSP00000361467.2	Q8TDM6-1
	DLG5	ENST00000424842.5	TSL:1	c.555-579G>C		intron	N/A	ENSP00000394797.1	A0A0A0MSL1
	DLG5	ENST00000459739.5	TSL:1	n.727-579G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37671 AN: 152056 Hom.: 5323 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.248 AC: 37690 AN: 152174 Hom.: 5330 Cov.: 32 AF XY: 0.253 AC XY: 18822 AN XY: 74378

African (AFR) AF: 0.129 AC: 5376 AN: 41540

American (AMR) AF: 0.384 AC: 5864 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1552 AN: 5166

South Asian (SAS) AF: 0.299 AC: 1440 AN: 4824

European-Finnish (FIN) AF: 0.310 AC: 3278 AN: 10590

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18780 AN: 67982

Other (OTH) AF: 0.246 AC: 520 AN: 2116

Alfa AF: 0.140 Hom.: 279

Bravo AF: 0.247

Asia WGS AF: 0.309 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.077
DANN	Benign	0.50
PhyloP100		-0.14
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: rs1270911; hg19: chr10-79578226;