chr18-3497716-T-C

Variant names:

• chr18-3497716-T-C
• rs10513868
• NM_004746.4:c.*1469A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

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 = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4	c.*1469A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000315677.8	NP_004737.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8	c.*1469A>G		3_prime_UTR_variant	Exon 13 of 13	5	NM_004746.4	ENSP00000316377.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.221 AC: 9186 AN: 41484

American (AMR) AF: 0.0798 AC: 1220 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 173 AN: 3472

East Asian (EAS) AF: 0.226 AC: 1173 AN: 5186

South Asian (SAS) AF: 0.119 AC: 575 AN: 4820

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10618

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0629 AC: 4276 AN: 68020

Other (OTH) AF: 0.118 AC: 249 AN: 2112

Alfa AF: 0.0782 Hom.: 1209

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
PhyloP100		0.68
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

Other links and lift over

dbSNP: rs10513868; hg19: chr18-3497714;