10-77926367-T-C

Variant names:

• chr10-77926367-T-C
• rs1846693029
• NM_004747.4:c.154A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004747.4(DLG5):​c.154A>G​(p.Lys52Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DLG5 NM_004747.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.41
• Publications: 0 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-AS1 (HGNC:45109): (DLG5 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	NM_004747.4	MANE Select	c.154A>G	p.Lys52Glu	missense	Exon 1 of 32	NP_004738.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	ENST00000372391.7	TSL:1 MANE Select	c.154A>G	p.Lys52Glu	missense	Exon 1 of 32	ENSP00000361467.2	Q8TDM6-1
	DLG5	ENST00000928380.1		c.154A>G	p.Lys52Glu	missense	Exon 1 of 32	ENSP00000598439.1
	DLG5	ENST00000928379.1		c.154A>G	p.Lys52Glu	missense	Exon 1 of 31	ENSP00000598438.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.037
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.59	D
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.4
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.10
Sift	Benign	0.074	T
Sift4G	Uncertain	0.011	D
Polyphen		0.32	B
Vest4		0.58
MutPred		0.21		Loss of ubiquitination at K52 (P = 0.0019)
MVP		0.50
MPC		1.8
ClinPred		0.95	D
GERP RS		3.7
PromoterAI		-0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.34
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs1846693029; hg19: chr10-79686125;