dbSNP rs3745051: DLGAP1:p.Pro517Pro (chr18-3729175-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_004746.4(DLGAP1):c.1551G>A(p.Pro517Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,612,722 control chromosomes in the GnomAD database, including 18,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.18 ( 3235 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14975 hom. )

Consequence

DLGAP1
NM_004746.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.480

Publications

15 publications found

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]

DLGAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 18-3729175-C-T is Benign according to our data. Variant chr18-3729175-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060604.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4 link	c.1551G>A	p.Pro517Pro	synonymous_variant	Exon 7 of 13	ENST00000315677.8	NP_004737.2	O14490-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP1	ENST00000315677.8 link	c.1551G>A	p.Pro517Pro	synonymous_variant	Exon 7 of 13	5	NM_004746.4	ENSP00000316377.3		O14490-1

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27791

AN:

151956

Hom.:

3232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.170

GnomAD2 exomes

AF:

0.163

AC:

40490

AN:

247898

AF XY:

0.161

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.335

Gnomad FIN exome

AF:

0.163

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.131

AC:

190888

AN:

1460646

Hom.:

14975

Cov.:

AF XY:

0.133

AC XY:

96739

AN XY:

726602

show subpopulations

African (AFR)

AF:

0.304

AC:

10190

AN:

33466

American (AMR)

AF:

0.137

AC:

6103

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4419

AN:

26090

East Asian (EAS)

AF:

0.337

AC:

13365

AN:

39672

South Asian (SAS)

AF:

0.219

AC:

18818

AN:

86098

European-Finnish (FIN)

AF:

0.150

AC:

7935

AN:

52998

Middle Eastern (MID)

AF:

0.227

AC:

1303

AN:

5730

European-Non Finnish (NFE)

AF:

0.107

AC:

119265

AN:

1111606

Other (OTH)

AF:

0.157

AC:

9490

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

10266

20532

30799

41065

51331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4678

9356

14034

18712

23390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.183

AC:

27812

AN:

152076

Hom.:

3235

Cov.:

AF XY:

0.185

AC XY:

13771

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.303

AC:

12549

AN:

41468

American (AMR)

AF:

0.141

AC:

2151

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

567

AN:

3472

East Asian (EAS)

AF:

0.346

AC:

1782

AN:

5146

South Asian (SAS)

AF:

0.224

AC:

1079

AN:

4822

European-Finnish (FIN)

AF:

0.165

AC:

1747

AN:

10582

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7446

AN:

67980

Other (OTH)

AF:

0.166

AC:

350

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1115

2230

3346

4461

5576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.128

Hom.:

2376

Bravo

AF:

0.186

Asia WGS

AF:

0.249

AC:

865

AN:

3478

EpiCase

AF:

0.119

EpiControl

AF:

0.112

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DLGAP1-related disorder

Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This 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

-0.41

CADD

Benign

6.9

(source)

DANN

Benign

0.68

PhyloP100

-0.48

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over