1-34913333-T-G

Variant names:

• chr1-34913333-T-G
• rs4652869
• NM_001080418.3:c.-134-5896A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001080418.3(DLGAP3):​c.-134-5896A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,052 control chromosomes in the GnomAD database, including 10,217 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 0.34 (10217 hom., cov: 32)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080418.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP3	NM_001080418.3	MANE Select	c.-134-5896A>C		intron	N/A	NP_001073887.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP3	ENST00000373347.6	TSL:5 MANE Select	c.-134-5896A>C		intron	N/A	ENSP00000362444.1
	DLGAP3	ENST00000495979.1	TSL:3	n.122-5896A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52150 AN: 151934 Hom.: 10210 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.343 AC: 52163 AN: 152052 Hom.: 10217 Cov.: 32 AF XY: 0.346 AC XY: 25742 AN XY: 74300

African (AFR) AF: 0.155 AC: 6449 AN: 41506

American (AMR) AF: 0.319 AC: 4876 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2432 AN: 5152

South Asian (SAS) AF: 0.498 AC: 2402 AN: 4820

European-Finnish (FIN) AF: 0.435 AC: 4597 AN: 10562

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28860 AN: 67958

Other (OTH) AF: 0.356 AC: 751 AN: 2110

Alfa AF: 0.395 Hom.: 54948

Bravo AF: 0.323

Asia WGS AF: 0.485 AC: 1684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.74
PhyloP100		0.51
Mutation Taster		=99/1	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: rs4652869; hg19: chr1-35378934;