Genetic Variant NM_004747.4:c.419A>C (chr10-77856847-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004747.4(DLG5):c.419A>C(p.Gln140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. Q140E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DLG5
NM_004747.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

85 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19880572).

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.419A>C	p.Gln140Pro	missense	Exon 3 of 32	NP_004738.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DLG5	ENST00000372391.7	TSL:1 MANE Select	c.419A>C	p.Gln140Pro	missense	Exon 3 of 32	ENSP00000361467.2
DLG5	ENST00000468332.6	TSL:2	n.194A>C		non_coding_transcript_exon	Exon 3 of 30	ENSP00000473298.1
DLG5	ENST00000475613.6	TSL:5	n.93+12252A>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.10

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.88

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.024

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

1.1

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.92

REVEL

Benign

0.068

Sift

Benign

0.033

Sift4G

Benign

0.16

Polyphen

0.16

Vest4

0.34

MutPred

0.61

Gain of glycosylation at T138 (P = 0.0552)

MVP

0.33

MPC

0.99

ClinPred

0.26

GERP RS

1.5

Varity_R

0.27

gMVP

0.61

Mutation Taster

=96/4

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over