rs1248674

Positions:

• chr10-77845338-A-C
• chr10-77845338-A-G
• chr10-77845338-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004747.4(DLG5):​c.865-1632T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,108 control chromosomes in the GnomAD database, including 44,101 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 0.75 (44093 hom., cov: 32)
  • Exomes 𝑓: 0.86 (8 hom.)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	NM_004747.4	c.865-1632T>G		intron_variant		ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.865-1632T>G		intron_variant		1	NM_004747.4	ENSP00000361467.2
DLG5	ENST00000468332.6	n.*94T>G		non_coding_transcript_exon_variant	6/30	2		ENSP00000473298.1
DLG5	ENST00000468332.6	n.*94T>G		3_prime_UTR_variant	6/30	2		ENSP00000473298.1
DLG5	ENST00000475613.6	n.94-14465T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114130 AN: 151968 Hom.: 44029 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.729

GnomAD4 exome AF: 0.864 AC: 19 AN: 22 Hom.: 8 Cov.: 0 AF XY: 0.889 AC XY: 16 AN XY: 18

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.813

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.751 AC: 114253 AN: 152086 Hom.: 44093 Cov.: 32 AF XY: 0.747 AC XY: 55527 AN XY: 74338

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.730

Alfa AF: 0.711 Hom.: 4925

Bravo AF: 0.773

Asia WGS AF: 0.770 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.79
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1248674; hg19: chr10-79605096;