1-34914463-C-T

Variant names:

• chr1-34914463-C-T
• rs6682829
• NM_001080418.3:c.-134-7026G>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.-134-7026G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,056 control chromosomes in the GnomAD database, including 11,207 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 0.35 (11207 hom., cov: 32)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080418.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP3	NM_001080418.3	MANE Select	c.-134-7026G>A		intron	N/A	NP_001073887.1	O95886

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP3	ENST00000373347.6	TSL:5 MANE Select	c.-134-7026G>A		intron	N/A	ENSP00000362444.1	O95886
	DLGAP3	ENST00000495979.1	TSL:3	n.122-7026G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53705 AN: 151938 Hom.: 11206 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.353 AC: 53704 AN: 152056 Hom.: 11207 Cov.: 32 AF XY: 0.359 AC XY: 26642 AN XY: 74306

African (AFR) AF: 0.123 AC: 5099 AN: 41512

American (AMR) AF: 0.388 AC: 5926 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1373 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3230 AN: 5156

South Asian (SAS) AF: 0.483 AC: 2324 AN: 4816

European-Finnish (FIN) AF: 0.443 AC: 4670 AN: 10544

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29861 AN: 67958

Other (OTH) AF: 0.371 AC: 783 AN: 2110

Alfa AF: 0.241 Hom.: 644

Bravo AF: 0.336

Asia WGS AF: 0.528 AC: 1835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.24
DANN	Benign	0.70
PhyloP100		-2.8
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6682829;

hg19: chr1-35380064;