1-34905129-A-AC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001080418.3(DLGAP3):c.254_255insG(p.Ser86Ter) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000725 in 1,559,274 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000079 (0 hom.)
• Consequence: DLGAP3 NM_001080418.3 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.89

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-34905129-A-AC is Benign according to our data. Variant chr1-34905129-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 757628.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP3	NM_001080418.3	c.254_255insG	p.Ser86Ter	frameshift_variant	3/12	ENST00000373347.6
DLGAP3	XM_011541879.3	c.254_255insG	p.Ser86Ter	frameshift_variant	4/13
DLGAP3	XM_047426631.1	c.254_255insG	p.Ser86Ter	frameshift_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP3	ENST00000373347.6	c.254_255insG	p.Ser86Ter	frameshift_variant	3/12	5	NM_001080418.3	P1
DLGAP3	ENST00000235180.4	c.254_255insG	p.Ser86Ter	frameshift_variant	1/10	2		P1
DLGAP3	ENST00000495979.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000787 AC: 111 AN: 1411050 Hom.: 0 Cov.: 33 AF XY: 0.0000789 AC XY: 55 AN XY: 697458

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000106

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.0000498

Gnomad4 FIN exome AF: 0.00190

Gnomad4 NFE exome AF: 0.00000645

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 148224 Hom.: 0 Cov.: 32 AF XY: 0.0000277 AC XY: 2 AN XY: 72176

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000134

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs762874947; hg19: chr1-35370730;