1-34888303-G-A

Position:

• chr1-34888303-G-A

Variant summary

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

The NM_001080418.3(DLGAP3):​c.1387-2018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 152,196 control chromosomes in the GnomAD database, including 371 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 0.052 (371 hom., cov: 32)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.1387-2018C>T		intron_variant		ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.1387-2018C>T		intron_variant			XP_011540181.1
DLGAP3	XM_011541880.3	c.-106+915C>T		intron_variant			XP_011540182.1
DLGAP3	XM_047426631.1	c.1387-2018C>T		intron_variant			XP_047282587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.1387-2018C>T		intron_variant		5	NM_001080418.3	ENSP00000362444	P1
DLGAP3	ENST00000235180.4	c.1387-2018C>T		intron_variant		2		ENSP00000235180	P1

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7974 AN: 152076 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0525 AC: 7990 AN: 152196 Hom.: 371 Cov.: 32 AF XY: 0.0551 AC XY: 4096 AN XY: 74400

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0869

Gnomad4 FIN AF: 0.0325

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0412 Hom.: 75

Bravo AF: 0.0574

Asia WGS AF: 0.124 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.71

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: rs7525948; hg19: chr1-35353904;