1-34903669-A-G

Variant names:

• chr1-34903669-A-G
• rs12120523
• NM_001080418.3:c.1107+608T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080418.3(DLGAP3):​c.1107+608T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,196 control chromosomes in the GnomAD database, including 1,029 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 0.11 (1029 hom., cov: 32)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.1107+608T>C		intron_variant	Intron 3 of 11	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.1107+608T>C		intron_variant	Intron 4 of 12		XP_011540181.1
DLGAP3	XM_047426631.1	c.1107+608T>C		intron_variant	Intron 3 of 11		XP_047282587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.1107+608T>C		intron_variant	Intron 3 of 11	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.1107+608T>C		intron_variant	Intron 1 of 9	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16006 AN: 152078 Hom.: 1028 Cov.: 32

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.105 AC: 16019 AN: 152196 Hom.: 1029 Cov.: 32 AF XY: 0.104 AC XY: 7743 AN XY: 74398

African (AFR) AF: 0.0515 AC: 2138 AN: 41546

American (AMR) AF: 0.0709 AC: 1084 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.116 AC: 559 AN: 4812

European-Finnish (FIN) AF: 0.135 AC: 1434 AN: 10590

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9958 AN: 67982

Other (OTH) AF: 0.101 AC: 214 AN: 2114

Alfa AF: 0.107 Hom.: 734

Bravo AF: 0.0983

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		-0.0060
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12120523; hg19: chr1-35369270;