1-34867325-G-C

Position:

• chr1-34867325-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080418.3(DLGAP3):​c.2578-134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,343,748 control chromosomes in the GnomAD database, including 77,074 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 0.28 (7863 hom., cov: 32)
  • Exomes 𝑓: 0.32 (69211 hom.)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.2578-134C>G		intron_variant		ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.2578-134C>G		intron_variant			XP_011540181.1
DLGAP3	XM_047426631.1	c.2578-134C>G		intron_variant			XP_047282587.1
DLGAP3	XM_011541880.3	c.1087-134C>G		intron_variant			XP_011540182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.2578-134C>G		intron_variant		5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.2578-134C>G		intron_variant		2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42732 AN: 151864 Hom.: 7847 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.318 AC: 378404 AN: 1191766 Hom.: 69211 AF XY: 0.323 AC XY: 194450 AN XY: 602940

Gnomad4 AFR exome AF: 0.0877

Gnomad4 AMR exome AF: 0.502

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.847

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.281 AC: 42770 AN: 151982 Hom.: 7863 Cov.: 32 AF XY: 0.297 AC XY: 22032 AN XY: 74286

Gnomad4 AFR AF: 0.0990

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.298

Alfa AF: 0.172 Hom.: 379

Bravo AF: 0.274

Asia WGS AF: 0.607 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.2
DANN	Benign	0.81

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

Publications

LitVar

Other links and lift over

dbSNP: rs1001616; hg19: chr1-35332926; COSMIC: COSV52391114;