3-197247312-C-T

Variant names:

• chr3-197247312-C-T
• rs373889
• NM_001366207.1:c.318+35367G>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+35367G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 151,920 control chromosomes in the GnomAD database, including 41,169 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 0.74 (41169 hom., cov: 30)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.318+35367G>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+35367G>A		intron_variant	Intron 4 of 24		NM_001366207.1	ENSP00000499414.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111621 AN: 151802 Hom.: 41139 Cov.: 30

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.735 AC: 111703 AN: 151920 Hom.: 41169 Cov.: 30 AF XY: 0.734 AC XY: 54458 AN XY: 74224

African (AFR) AF: 0.716 AC: 29626 AN: 41392

American (AMR) AF: 0.715 AC: 10924 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2717 AN: 3472

East Asian (EAS) AF: 0.814 AC: 4204 AN: 5162

South Asian (SAS) AF: 0.761 AC: 3655 AN: 4804

European-Finnish (FIN) AF: 0.689 AC: 7274 AN: 10558

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50814 AN: 67946

Other (OTH) AF: 0.731 AC: 1540 AN: 2108

Alfa AF: 0.743 Hom.: 20321

Bravo AF: 0.737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.51
PhyloP100		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs373889; hg19: chr3-196974183;