rs10513868

Positions:

• chr18-3497716-T-C

Variant summary

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

The NM_004746.4(DLGAP1):​c.*1469A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,206 control chromosomes in the GnomAD database, including 1,484 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 0.12 (1484 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLGAP1 NM_004746.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.*1469A>G		3_prime_UTR_variant	13/13	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.*1469A>G		3_prime_UTR_variant	13/13	5	NM_004746.4	ENSP00000316377	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18212 AN: 152088 Hom.: 1473 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.0498

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0628

Gnomad OTH AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.120 AC: 18268 AN: 152206 Hom.: 1484 Cov.: 33 AF XY: 0.124 AC XY: 9201 AN XY: 74426

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.0798

Gnomad4 ASJ AF: 0.0498

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0629

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0722 Hom.: 730

Bravo AF: 0.121

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.1
DANN	Benign	0.44

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: rs10513868; hg19: chr18-3497714;