Genetic Variant NM_004747.4:c.865-3908C>T (chr10-77847614-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004747.4(DLG5):c.865-3908C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,078 control chromosomes in the GnomAD database, including 5,498 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 ( 5498 hom., cov: 32)

Consequence

DLG5
NM_004747.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.129

Publications

9 publications found

Variant links:

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

DLG5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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 rank	MANE	Protein	UniProt
DLG5	NM_004747.4 link	c.865-3908C>T		intron_variant	Intron 5 of 31	ENST00000372391.7	NP_004738.3	Q8TDM6-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLG5	ENST00000372391.7 link	c.865-3908C>T	intron_variant	Intron 5 of 31	1	NM_004747.4	ENSP00000361467.2	Q8TDM6-1
DLG5	ENST00000468332.6 link	n.640-2177C>T	intron_variant	Intron 5 of 29	2		ENSP00000473298.1	R4GMQ2
DLG5	ENST00000475613.6 link	n.94-16741C>T	intron_variant	Intron 1 of 21	5

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38728

AN:

151960

Hom.:

5490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.176

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:

0.278

Gnomad OTH

AF:

0.239

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

GnomAD4 genome

AF:

0.255

AC:

38743

AN:

152078

Hom.:

5498

Cov.:

AF XY:

0.260

AC XY:

19328

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.152

AC:

6323

AN:

41488

American (AMR)

AF:

0.387

AC:

5911

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

616

AN:

3470

East Asian (EAS)

AF:

0.308

AC:

1591

AN:

5166

South Asian (SAS)

AF:

0.299

AC:

1441

AN:

4814

European-Finnish (FIN)

AF:

0.309

AC:

3268

AN:

10582

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18863

AN:

67968

Other (OTH)

AF:

0.237

AC:

499

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1422

2844

4266

5688

7110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.271

Hom.:

9773

Bravo

AF:

0.255

Asia WGS

AF:

0.321

AC:

1119

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.82

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over