3-197200310-T-G

Variant names:

• chr3-197200310-T-G
• rs7650753
• NM_001366207.1:c.319-5721A>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.319-5721A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,968 control chromosomes in the GnomAD database, including 25,932 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 0.58 (25932 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366207.1. 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
	DLG1	NM_001366207.1	MANE Select	c.319-5721A>C		intron	N/A	NP_001353136.1
	DLG1	NM_004087.2		c.319-5721A>C		intron	N/A	NP_004078.2
	DLG1	NM_001366214.1		c.319-5721A>C		intron	N/A	NP_001353143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG1	ENST00000667157.1	MANE Select	c.319-5721A>C		intron	N/A	ENSP00000499414.1
	DLG1	ENST00000346964.6	TSL:1	c.319-5721A>C		intron	N/A	ENSP00000345731.2
	DLG1	ENST00000419354.5	TSL:1	c.319-5721A>C		intron	N/A	ENSP00000407531.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88171 AN: 151854 Hom.: 25923 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.580 AC: 88215 AN: 151968 Hom.: 25932 Cov.: 32 AF XY: 0.579 AC XY: 42979 AN XY: 74252

African (AFR) AF: 0.507 AC: 21003 AN: 41452

American (AMR) AF: 0.600 AC: 9166 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2049 AN: 3466

East Asian (EAS) AF: 0.788 AC: 4087 AN: 5184

South Asian (SAS) AF: 0.705 AC: 3390 AN: 4810

European-Finnish (FIN) AF: 0.524 AC: 5530 AN: 10554

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 40990 AN: 67914

Other (OTH) AF: 0.580 AC: 1222 AN: 2108

Alfa AF: 0.513 Hom.: 2164

Bravo AF: 0.583

Asia WGS AF: 0.703 AC: 2445 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.098
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: rs7650753; hg19: chr3-196927181;