rs12141243

Positions:

• chr1-34881321-T-C

Variant summary

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

The NM_001080418.3(DLGAP3):​c.2000+3657A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 152,248 control chromosomes in the GnomAD database, including 937 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 0.098 (937 hom., cov: 32)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.2000+3657A>G		intron_variant		ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.2000+3657A>G		intron_variant			XP_011540181.1
DLGAP3	XM_011541880.3	c.509+3657A>G		intron_variant			XP_011540182.1
DLGAP3	XM_047426631.1	c.2000+3657A>G		intron_variant			XP_047282587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.2000+3657A>G		intron_variant		5	NM_001080418.3	ENSP00000362444	P1
DLGAP3	ENST00000235180.4	c.2000+3657A>G		intron_variant		2		ENSP00000235180	P1

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14837 AN: 152130 Hom.: 933 Cov.: 32

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0976 AC: 14853 AN: 152248 Hom.: 937 Cov.: 32 AF XY: 0.0969 AC XY: 7215 AN XY: 74432

Gnomad4 AFR AF: 0.0382

Gnomad4 AMR AF: 0.0788

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.102

Alfa AF: 0.113 Hom.: 251

Bravo AF: 0.0900

Asia WGS AF: 0.100 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.89

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: rs12141243; hg19: chr1-35346922;