3-197227576-T-G

Position:

• chr3-197227576-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366207.1(DLG1):​c.319-32987A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,072 control chromosomes in the GnomAD database, including 24,619 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 0.56 (24619 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.319-32987A>C		intron_variant		ENST00000667157.1	NP_001353136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG1	ENST00000667157.1	c.319-32987A>C		intron_variant			NM_001366207.1	ENSP00000499414.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85518 AN: 151954 Hom.: 24613 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.563 AC: 85558 AN: 152072 Hom.: 24619 Cov.: 32 AF XY: 0.562 AC XY: 41747 AN XY: 74344

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.568

Alfa AF: 0.487 Hom.: 1845

Bravo AF: 0.562

Asia WGS AF: 0.700 AC: 2438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs2122824; hg19: chr3-196954447;