1-34900455-C-T

Variant names:

• chr1-34900455-C-T
• rs1931059
• NM_001080418.3:c.1108-182G>A

Variant summary

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

The NM_001080418.3(DLGAP3):​c.1108-182G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,204 control chromosomes in the GnomAD database, including 5,761 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 0.22 (5761 hom., cov: 32)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795
• Publications: 9 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.1108-182G>A		intron_variant	Intron 3 of 11	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.1108-182G>A		intron_variant	Intron 4 of 12		XP_011540181.1
DLGAP3	XM_047426631.1	c.1108-182G>A		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.1108-182G>A		intron_variant	Intron 3 of 11	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.1108-182G>A		intron_variant	Intron 1 of 9	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33681 AN: 152084 Hom.: 5756 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.221 AC: 33694 AN: 152204 Hom.: 5761 Cov.: 32 AF XY: 0.236 AC XY: 17597 AN XY: 74412

African (AFR) AF: 0.0869 AC: 3611 AN: 41548

American (AMR) AF: 0.390 AC: 5966 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3472

East Asian (EAS) AF: 0.913 AC: 4711 AN: 5162

South Asian (SAS) AF: 0.428 AC: 2062 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2737 AN: 10578

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13074 AN: 68006

Other (OTH) AF: 0.259 AC: 547 AN: 2112

Alfa AF: 0.202 Hom.: 2569

Bravo AF: 0.223

Asia WGS AF: 0.607 AC: 2108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1931059; hg19: chr1-35366056;