3-197258725-C-T

Variant names:

• chr3-197258725-C-T
• rs9843659
• NM_001366207.1:c.318+23954G>A

Variant summary

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

The NM_001366207.1(DLG1):​c.318+23954G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,022 control chromosomes in the GnomAD database, including 24,523 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 0.57 (24523 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.318+23954G>A		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.318+23954G>A		intron_variant	Intron 4 of 24		NM_001366207.1	ENSP00000499414.1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85919 AN: 151904 Hom.: 24502 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.566 AC: 85984 AN: 152022 Hom.: 24523 Cov.: 32 AF XY: 0.562 AC XY: 41735 AN XY: 74308

African (AFR) AF: 0.628 AC: 26048 AN: 41474

American (AMR) AF: 0.541 AC: 8257 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1726 AN: 3466

East Asian (EAS) AF: 0.700 AC: 3618 AN: 5166

South Asian (SAS) AF: 0.388 AC: 1873 AN: 4828

European-Finnish (FIN) AF: 0.522 AC: 5504 AN: 10540

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.546 AC: 37132 AN: 67964

Other (OTH) AF: 0.536 AC: 1130 AN: 2110

Alfa AF: 0.543 Hom.: 38115

Bravo AF: 0.572

Asia WGS AF: 0.550 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.3
DANN	Benign	0.43
PhyloP100		0.47
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: rs9843659; hg19: chr3-196985596;