10-77811115-G-T

Position:

• chr10-77811115-G-T

Variant summary

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

The NM_004747.4(DLG5):​c.4442C>A​(p.Pro1481Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0434 in 1,610,818 control chromosomes in the GnomAD database, including 2,215 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.044 (232 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1983 hom.)
• Consequence: DLG5 NM_004747.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

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 (MetaRNN=0.0017066598).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	NM_004747.4	c.4442C>A	p.Pro1481Gln	missense_variant	23/32	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.4442C>A	p.Pro1481Gln	missense_variant	23/32	1	NM_004747.4	ENSP00000361467.2

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6743 AN: 151826 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.0414

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.0451

GnomAD3 exomes AF: 0.0573 AC: 14266 AN: 248976 Hom.: 633 AF XY: 0.0574 AC XY: 7737 AN XY: 134798

Gnomad AFR exome AF: 0.0350

Gnomad AMR exome AF: 0.0438

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.0531

Gnomad FIN exome AF: 0.0451

Gnomad NFE exome AF: 0.0415

Gnomad OTH exome AF: 0.0612

GnomAD4 exome AF: 0.0433 AC: 63113 AN: 1458876 Hom.: 1983 Cov.: 32 AF XY: 0.0441 AC XY: 32015 AN XY: 725752

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.0462

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.0516

Gnomad4 FIN exome AF: 0.0446

Gnomad4 NFE exome AF: 0.0349

Gnomad4 OTH exome AF: 0.0576

GnomAD4 genome AF: 0.0444 AC: 6753 AN: 151942 Hom.: 232 Cov.: 32 AF XY: 0.0448 AC XY: 3326 AN XY: 74262

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.0476

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.0632

Gnomad4 FIN AF: 0.0414

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0475

Alfa AF: 0.0463 Hom.: 500

Bravo AF: 0.0471

TwinsUK AF: 0.0375 AC: 139

ALSPAC AF: 0.0309 AC: 119

ESP6500AA AF: 0.0304 AC: 134

ESP6500EA AF: 0.0422 AC: 363

ExAC AF: 0.0573 AC: 6953

EpiCase AF: 0.0411

EpiControl AF: 0.0392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.20	.;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.86
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.0	.;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.083
Sift	Benign	0.10	T;T
Sift4G	Uncertain	0.053	T;T
Polyphen		0.0	.;B
Vest4		0.066
MPC		0.22
ClinPred		0.011	T
GERP RS		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.030
gMVP		0.29

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: rs2289310; hg19: chr10-79570873; COSMIC: COSV64947544; COSMIC: COSV64947544;