3-197295369-A-T

Variant names:

• chr3-197295369-A-T
• rs3915512
• NM_001366207.1:c.151+977T>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001366207.1(DLG1):​c.151+977T>A 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 152,070 control chromosomes in the GnomAD database, including 5,668 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 (5668 hom., cov: 32)
• Consequence: DLG1 NM_001366207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG1	NM_001366207.1	c.151+977T>A		intron_variant	Intron 3 of 24	ENST00000667157.1	NP_001353136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG1	ENST00000667157.1	c.151+977T>A		intron_variant	Intron 3 of 24		NM_001366207.1	ENSP00000499414.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36934 AN: 151952 Hom.: 5671 Cov.: 32

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.243 AC: 36938 AN: 152070 Hom.: 5668 Cov.: 32 AF XY: 0.247 AC XY: 18383 AN XY: 74332

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.234

Alfa AF: 0.154 Hom.: 343

Bravo AF: 0.240

Asia WGS AF: 0.443 AC: 1536 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.27		Position offset: 39

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3915512; hg19: chr3-197022240;