rs16837122

Positions:

• chr1-34912977-C-G
• chr1-34912977-C-T

Variant summary

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

The NM_001080418.3(DLGAP3):​c.-134-5540G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,194 control chromosomes in the GnomAD database, including 2,808 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 0.19 (2808 hom., cov: 32)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP3	NM_001080418.3	c.-134-5540G>C		intron_variant		ENST00000373347.6
DLGAP3	XM_011541879.3	c.-134-5540G>C		intron_variant
DLGAP3	XM_047426631.1	c.-134-5540G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP3	ENST00000373347.6	c.-134-5540G>C		intron_variant		5	NM_001080418.3	P1
DLGAP3	ENST00000495979.1	n.122-5540G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28504 AN: 152076 Hom.: 2803 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.187 AC: 28528 AN: 152194 Hom.: 2808 Cov.: 32 AF XY: 0.186 AC XY: 13821 AN XY: 74414

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0150

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.214

Alfa AF: 0.0904 Hom.: 114

Bravo AF: 0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.74

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: rs16837122; hg19: chr1-35378578;