chr1-34885670-GC-G

Position:

• chr1-34885670-GC-G

Variant summary

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

The NM_001080418.3(DLGAP3):​c.1721del​(p.Gly574AlafsTer104) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLGAP3 NM_001080418.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.1721del	p.Gly574AlafsTer104	frameshift_variant	7/12	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.1721del	p.Gly574AlafsTer104	frameshift_variant	8/13		XP_011540181.1
DLGAP3	XM_047426631.1	c.1721del	p.Gly574AlafsTer104	frameshift_variant	7/12		XP_047282587.1
DLGAP3	XM_011541880.3	c.230del	p.Gly77AlafsTer104	frameshift_variant	3/8		XP_011540182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.1721del	p.Gly574AlafsTer104	frameshift_variant	7/12	5	NM_001080418.3	ENSP00000362444	P1
DLGAP3	ENST00000235180.4	c.1721del	p.Gly574AlafsTer104	frameshift_variant	5/10	2		ENSP00000235180	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs35688758; hg19: chr1-35351271;