Menu
GeneBe

10-77794057-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_004747.4(DLG5):c.5607G>A(p.Gln1869=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,208 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 35 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 34 hom. )

Consequence

DLG5
NM_004747.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0780
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-77794057-C-T is Benign according to our data. Variant chr10-77794057-C-T is described in ClinVar as [Benign]. Clinvar id is 778464.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.078 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1642/152350) while in subpopulation AFR AF= 0.037 (1538/41580). AF 95% confidence interval is 0.0355. There are 35 homozygotes in gnomad4. There are 747 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1628 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DLG5NM_004747.4 linkuse as main transcriptc.5607G>A p.Gln1869= synonymous_variant 31/32 ENST00000372391.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DLG5ENST00000372391.7 linkuse as main transcriptc.5607G>A p.Gln1869= synonymous_variant 31/321 NM_004747.4 P1Q8TDM6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0107
AC:
1628
AN:
152232
Hom.:
33
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0368
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00908
GnomAD3 exomes
AF:
0.00266
AC:
668
AN:
251454
Hom.:
11
AF XY:
0.00201
AC XY:
273
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.0352
Gnomad AMR exome
AF:
0.00197
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.000977
GnomAD4 exome
AF:
0.00114
AC:
1662
AN:
1461858
Hom.:
34
Cov.:
32
AF XY:
0.00101
AC XY:
731
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0365
Gnomad4 AMR exome
AF:
0.00203
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000142
Gnomad4 OTH exome
AF:
0.00278
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0108
AC:
1642
AN:
152350
Hom.:
35
Cov.:
33
AF XY:
0.0100
AC XY:
747
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0370
Gnomad4 AMR
AF:
0.00457
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00899
Alfa
AF:
0.00566
Hom.:
4
Bravo
AF:
0.0121
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
5.9
Dann
Benign
0.81

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1058199; hg19: chr10-79553815; API