1-34875047-A-G

Variant summary

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

The NM_001080418.3(DLGAP3):c.2001-5958T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,032 control chromosomes in the GnomAD database, including 54,255 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 0.83 (54255 hom., cov: 31)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

Genes affected

DLGAP3 (HGNC:30368): (DLG associated protein 3) Predicted to enable PDZ domain binding activity; molecular adaptor activity; and scaffold protein binding activity. Predicted to be involved in protein-containing complex assembly and regulation of postsynaptic neurotransmitter receptor activity. Predicted to be located in synapse. Predicted to be part of postsynaptic density. Predicted to be active in several cellular components, including cholinergic synapse; glutamatergic synapse; and neuromuscular junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP3	NM_001080418.3	c.2001-5958T>C		intron_variant		ENST00000373347.6
DLGAP3	XM_011541879.3	c.2001-5958T>C		intron_variant
DLGAP3	XM_011541880.3	c.510-5958T>C		intron_variant
DLGAP3	XM_047426631.1	c.2001-5958T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP3	ENST00000373347.6	c.2001-5958T>C		intron_variant		5	NM_001080418.3	P1
DLGAP3	ENST00000235180.4	c.2001-5958T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126818 AN: 151914 Hom.: 54249 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.834 AC: 126859 AN: 152032 Hom.: 54255 Cov.: 31 AF XY: 0.835 AC XY: 62048 AN XY: 74310

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.948

Gnomad4 NFE AF: 0.934

Gnomad4 OTH AF: 0.838

Alfa AF: 0.897 Hom.: 28034

Bravo AF: 0.815

Asia WGS AF: 0.851 AC: 2960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.2
Dann	Benign	0.46

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: rs4653112; hg19: chr1-35340648;