NM_001080418.3:c.-134-840C>A

Variant names:

• chr1-34908277-G-T
• rs7555884
• NM_001080418.3:c.-134-840C>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.-134-840C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,086 control chromosomes in the GnomAD database, including 20,976 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 0.52 (20976 hom., cov: 33)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.-134-840C>A		intron_variant	Intron 1 of 11	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.-134-840C>A		intron_variant	Intron 2 of 12		XP_011540181.1
DLGAP3	XM_047426631.1	c.-134-840C>A		intron_variant	Intron 1 of 11		XP_047282587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.-134-840C>A		intron_variant	Intron 1 of 11	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000495979.1	n.122-840C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78623 AN: 151968 Hom.: 20965 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.517 AC: 78668 AN: 152086 Hom.: 20976 Cov.: 33 AF XY: 0.515 AC XY: 38265 AN XY: 74342

African (AFR) AF: 0.397 AC: 16453 AN: 41460

American (AMR) AF: 0.431 AC: 6589 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1864 AN: 3472

East Asian (EAS) AF: 0.495 AC: 2558 AN: 5172

South Asian (SAS) AF: 0.621 AC: 3000 AN: 4834

European-Finnish (FIN) AF: 0.549 AC: 5802 AN: 10576

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40603 AN: 67960

Other (OTH) AF: 0.518 AC: 1095 AN: 2114

Alfa AF: 0.571 Hom.: 66187

Bravo AF: 0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.54
PhyloP100		-0.88
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: rs7555884; hg19: chr1-35373878;