3-197234315-A-G

Variant names:

• chr3-197234315-A-G
• rs10489880
• NM_001366207.1:c.319-39726T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366207.1(DLG1):​c.319-39726T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,194 control chromosomes in the GnomAD database, including 5,659 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 0.24 (5659 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 8 publications found

Genes affected

DLG1 (HGNC:2900): (discs large MAGUK scaffold protein 1) This gene encodes a multi-domain scaffolding protein that is required for normal development. This protein may have a role in septate junction formation, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. A multitude of transcript variants deriving from alternative splicing and the use of multiple alternate promoter have been observed, including some splice variants that may be specific to brain and other tissues. An upstream uORF may regulate translation at some splice variants of this gene. [provided by RefSeq, Sep 2018]

DLG1 Gene-Disease associations (from GenCC):

• Brugada syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.319-39726T>C		intron_variant	Intron 4 of 24	ENST00000667157.1	NP_001353136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG1	ENST00000667157.1	c.319-39726T>C		intron_variant	Intron 4 of 24		NM_001366207.1	ENSP00000499414.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36909 AN: 152076 Hom.: 5660 Cov.: 32

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.243 AC: 36914 AN: 152194 Hom.: 5659 Cov.: 32 AF XY: 0.246 AC XY: 18304 AN XY: 74414

African (AFR) AF: 0.0947 AC: 3937 AN: 41556

American (AMR) AF: 0.312 AC: 4764 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3468

East Asian (EAS) AF: 0.713 AC: 3692 AN: 5176

South Asian (SAS) AF: 0.279 AC: 1345 AN: 4828

European-Finnish (FIN) AF: 0.291 AC: 3076 AN: 10578

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18698 AN: 67984

Other (OTH) AF: 0.233 AC: 493 AN: 2114

Alfa AF: 0.272 Hom.: 6595

Bravo AF: 0.241

Asia WGS AF: 0.440 AC: 1528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.2
DANN	Benign	0.72
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs10489880; hg19: chr3-196961186;