rs1248689

Positions:

• chr10-77851629-T-C

Variant summary

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

The NM_004747.4(DLG5):​c.864+1725A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,052 control chromosomes in the GnomAD database, including 5,490 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 (5490 hom., cov: 32)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	NM_004747.4	c.864+1725A>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.864+1725A>G		intron_variant		1	NM_004747.4	ENSP00000361467	P1
DLG5	ENST00000468332.6	c.639+1725A>G		intron_variant, NMD_transcript_variant		2		ENSP00000473298
DLG5	ENST00000475613.6	n.93+17470A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38663 AN: 151932 Hom.: 5482 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.254 AC: 38677 AN: 152052 Hom.: 5490 Cov.: 32 AF XY: 0.260 AC XY: 19291 AN XY: 74330

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.236

Alfa AF: 0.263 Hom.: 704

Bravo AF: 0.254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
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: rs1248689; hg19: chr10-79611387;