rs1058198

Variant names:

• chr10-77806874-G-A
• rs1058198
• NM_004747.4:c.4851C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-77806874-G-A
• chr10-77806874-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004747.4(DLG5):​c.4851C>T​(p.Asp1617Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,613,428 control chromosomes in the GnomAD database, including 87,643 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 0.30 (7271 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80372 hom.)
• Consequence: DLG5 NM_004747.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 30 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):

• Yuksel-Vogel-Bauer syndrome

  Inheritance: AD, AR Classification: LIMITED Submitted by: G2P
• ciliopathy

  Inheritance: AR, AD Classification: LIMITED Submitted by: Franklin by Genoox
• congenital anomaly of kidney and urinary tract

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-1.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	NM_004747.4	MANE Select	c.4851C>T	p.Asp1617Asp	synonymous	Exon 26 of 32	NP_004738.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	ENST00000372391.7	TSL:1 MANE Select	c.4851C>T	p.Asp1617Asp	synonymous	Exon 26 of 32	ENSP00000361467.2
	DLG5	ENST00000424842.5	TSL:1	c.1734C>T	p.Asp578Asp	synonymous	Exon 14 of 20	ENSP00000394797.1
	DLG5	ENST00000459739.5	TSL:1	n.1898C>T		non_coding_transcript_exon	Exon 12 of 17

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46250 AN: 151906 Hom.: 7271 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.300 AC: 75456 AN: 251426 AF XY: 0.304

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.185

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.348

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.329 AC: 480910 AN: 1461404 Hom.: 80372 Cov.: 55 AF XY: 0.328 AC XY: 238719 AN XY: 726932

African (AFR) AF: 0.270 AC: 9052 AN: 33472

American (AMR) AF: 0.245 AC: 10947 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 9426 AN: 26126

East Asian (EAS) AF: 0.215 AC: 8527 AN: 39696

South Asian (SAS) AF: 0.282 AC: 24329 AN: 86220

European-Finnish (FIN) AF: 0.272 AC: 14518 AN: 53410

Middle Eastern (MID) AF: 0.323 AC: 1861 AN: 5766

European-Non Finnish (NFE) AF: 0.345 AC: 383111 AN: 1111624

Other (OTH) AF: 0.317 AC: 19139 AN: 60374

GnomAD4 genome AF: 0.304 AC: 46252 AN: 152024 Hom.: 7271 Cov.: 32 AF XY: 0.301 AC XY: 22360 AN XY: 74298

African (AFR) AF: 0.262 AC: 10856 AN: 41478

American (AMR) AF: 0.269 AC: 4120 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3468

East Asian (EAS) AF: 0.189 AC: 976 AN: 5164

South Asian (SAS) AF: 0.287 AC: 1385 AN: 4820

European-Finnish (FIN) AF: 0.259 AC: 2736 AN: 10560

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23622 AN: 67926

Other (OTH) AF: 0.323 AC: 683 AN: 2112

Alfa AF: 0.336 Hom.: 14143

Bravo AF: 0.303

Asia WGS AF: 0.255 AC: 890 AN: 3478

EpiCase AF: 0.362

EpiControl AF: 0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.019
DANN	Benign	0.62
PhyloP100		-1.3
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1058198; hg19: chr10-79566632; COSMIC: COSV64947660;