10-77791882-C-T

Position:

• chr10-77791882-C-T

Variant summary

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

The NM_004747.4(DLG5):​c.*558G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 154,080 control chromosomes in the GnomAD database, including 5,855 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 0.26 (5777 hom., cov: 33)
  • Exomes 𝑓: 0.27 (78 hom.)
• Consequence: DLG5 NM_004747.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.16

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]

ENSG00000228748 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	NM_004747.4	c.*558G>A		3_prime_UTR_variant	32/32	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.*558G>A		3_prime_UTR_variant	32/32	1	NM_004747.4	ENSP00000361467.2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39983 AN: 152026 Hom.: 5766 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.267 AC: 517 AN: 1936 Hom.: 78 Cov.: 0 AF XY: 0.268 AC XY: 273 AN XY: 1018

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.263 AC: 40020 AN: 152144 Hom.: 5777 Cov.: 33 AF XY: 0.268 AC XY: 19930 AN XY: 74382

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.265

Alfa AF: 0.265 Hom.: 5514

Bravo AF: 0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.076
DANN	Benign	0.50

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: rs2165047; hg19: chr10-79551640; COSMIC: COSV64947657; COSMIC: COSV64947657;