1-34898856-T-G

Variant names:

• chr1-34898856-T-G
• rs4259608
• NM_001080418.3:c.1386+813A>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.1386+813A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,092 control chromosomes in the GnomAD database, including 6,837 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 0.25 (6837 hom., cov: 32)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.1386+813A>C		intron_variant	Intron 5 of 11	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.1386+813A>C		intron_variant	Intron 6 of 12		XP_011540181.1
DLGAP3	XM_047426631.1	c.1386+813A>C		intron_variant	Intron 5 of 11		XP_047282587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.1386+813A>C		intron_variant	Intron 5 of 11	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.1386+813A>C		intron_variant	Intron 3 of 9	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38756 AN: 151972 Hom.: 6831 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.255 AC: 38772 AN: 152092 Hom.: 6837 Cov.: 32 AF XY: 0.270 AC XY: 20073 AN XY: 74314

African (AFR) AF: 0.117 AC: 4861 AN: 41510

American (AMR) AF: 0.414 AC: 6322 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3466

East Asian (EAS) AF: 0.915 AC: 4726 AN: 5164

South Asian (SAS) AF: 0.435 AC: 2093 AN: 4814

European-Finnish (FIN) AF: 0.307 AC: 3240 AN: 10556

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15829 AN: 67982

Other (OTH) AF: 0.286 AC: 602 AN: 2108

Alfa AF: 0.244 Hom.: 8429

Bravo AF: 0.254

Asia WGS AF: 0.616 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.020
DANN	Benign	0.63
PhyloP100		-1.2
Mutation Taster		=100/0	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: rs4259608; hg19: chr1-35364457;