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GeneBe

18-3534324-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_004746.4(DLGAP1):c.2349C>T(p.Ala783=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,614,126 control chromosomes in the GnomAD database, including 346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 54 hom., cov: 32)
Exomes 𝑓: 0.018 ( 292 hom. )

Consequence

DLGAP1
NM_004746.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.548
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-3534324-G-A is Benign according to our data. Variant chr18-3534324-G-A is described in ClinVar as [Benign]. Clinvar id is 3056276.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.548 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0226 (3448/152262) while in subpopulation AFR AF= 0.0377 (1564/41536). AF 95% confidence interval is 0.0361. There are 54 homozygotes in gnomad4. There are 1737 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 3438 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DLGAP1NM_004746.4 linkuse as main transcriptc.2349C>T p.Ala783= synonymous_variant 10/13 ENST00000315677.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DLGAP1ENST00000315677.8 linkuse as main transcriptc.2349C>T p.Ala783= synonymous_variant 10/135 NM_004746.4 P1O14490-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0226
AC:
3438
AN:
152144
Hom.:
53
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0376
Gnomad AMI
AF:
0.00659
Gnomad AMR
AF:
0.0162
Gnomad ASJ
AF:
0.00980
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.0292
Gnomad FIN
AF:
0.0261
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.0164
Gnomad OTH
AF:
0.0215
GnomAD3 exomes
AF:
0.0173
AC:
4358
AN:
251270
Hom.:
55
AF XY:
0.0180
AC XY:
2445
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.0382
Gnomad AMR exome
AF:
0.00807
Gnomad ASJ exome
AF:
0.0126
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0306
Gnomad FIN exome
AF:
0.0234
Gnomad NFE exome
AF:
0.0158
Gnomad OTH exome
AF:
0.0150
GnomAD4 exome
AF:
0.0178
AC:
26085
AN:
1461864
Hom.:
292
Cov.:
33
AF XY:
0.0184
AC XY:
13369
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0381
Gnomad4 AMR exome
AF:
0.00885
Gnomad4 ASJ exome
AF:
0.0129
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.0297
Gnomad4 FIN exome
AF:
0.0213
Gnomad4 NFE exome
AF:
0.0172
Gnomad4 OTH exome
AF:
0.0190
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0226
AC:
3448
AN:
152262
Hom.:
54
Cov.:
32
AF XY:
0.0233
AC XY:
1737
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0377
Gnomad4 AMR
AF:
0.0162
Gnomad4 ASJ
AF:
0.00980
Gnomad4 EAS
AF:
0.000965
Gnomad4 SAS
AF:
0.0297
Gnomad4 FIN
AF:
0.0261
Gnomad4 NFE
AF:
0.0165
Gnomad4 OTH
AF:
0.0217
Alfa
AF:
0.0188
Hom.:
21
Bravo
AF:
0.0228
Asia WGS
AF:
0.0180
AC:
63
AN:
3478
EpiCase
AF:
0.0164
EpiControl
AF:
0.0162

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

DLGAP1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 20, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
Cadd
Benign
10
Dann
Benign
0.76

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35715722; hg19: chr18-3534322; API