1-34876494-G-A

Variant names:

• chr1-34876494-G-A
• rs11264126
• NM_001080418.3:c.2001-7405C>T

Variant summary

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

The NM_001080418.3(DLGAP3):​c.2001-7405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,068 control chromosomes in the GnomAD database, including 13,726 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 0.41 (13726 hom., cov: 32)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.2001-7405C>T		intron_variant	Intron 8 of 11	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.2001-7405C>T		intron_variant	Intron 9 of 12		XP_011540181.1
DLGAP3	XM_047426631.1	c.2001-7405C>T		intron_variant	Intron 8 of 11		XP_047282587.1
DLGAP3	XM_011541880.3	c.510-7405C>T		intron_variant	Intron 4 of 7		XP_011540182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.2001-7405C>T		intron_variant	Intron 8 of 11	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.2001-7405C>T		intron_variant	Intron 6 of 9	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62982 AN: 151950 Hom.: 13715 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.414 AC: 63012 AN: 152068 Hom.: 13726 Cov.: 32 AF XY: 0.427 AC XY: 31773 AN XY: 74340

African (AFR) AF: 0.322 AC: 13337 AN: 41476

American (AMR) AF: 0.434 AC: 6634 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1543 AN: 3464

East Asian (EAS) AF: 0.760 AC: 3928 AN: 5170

South Asian (SAS) AF: 0.505 AC: 2434 AN: 4818

European-Finnish (FIN) AF: 0.569 AC: 6015 AN: 10566

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27761 AN: 67962

Other (OTH) AF: 0.429 AC: 905 AN: 2110

Alfa AF: 0.408 Hom.: 36464

Bravo AF: 0.399

Asia WGS AF: 0.600 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		0.55
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: rs11264126; hg19: chr1-35342095;