Genetic Variant DLGAP1:p.Thr361Thr (chr18-3814148-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004746.4(DLGAP1):c.1083G>C(p.Thr361Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 1,613,844 control chromosomes in the GnomAD database, including 4,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.10 ( 1503 hom., cov: 31)

Exomes 𝑓: 0.044 ( 2758 hom. )

Consequence

DLGAP1
NM_004746.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.190

Publications

13 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 18-3814148-C-G is Benign according to our data. Variant chr18-3814148-C-G is described in ClinVar as Benign. ClinVar VariationId is 3060984.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP1	NM_004746.4 link	c.1083G>C	p.Thr361Thr	synonymous_variant	Exon 5 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.1083G>C	p.Thr361Thr	synonymous_variant	Exon 5 of 13	5	NM_004746.4	ENSP00000316377.3		O14490-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15528

AN:

151860

Hom.:

1498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0758

Gnomad ASJ

AF:

0.0791

Gnomad EAS

AF:

0.0615

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0545

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0296

Gnomad OTH

AF:

0.0786

GnomAD2 exomes

AF:

0.0672

AC:

16871

AN:

251036

AF XY:

0.0652

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.0689

Gnomad ASJ exome

AF:

0.0770

Gnomad EAS exome

AF:

0.0662

Gnomad FIN exome

AF:

0.0507

Gnomad NFE exome

AF:

0.0303

Gnomad OTH exome

AF:

0.0583

GnomAD4 exome

AF:

0.0445

AC:

65048

AN:

1461866

Hom.:

2758

Cov.:

AF XY:

0.0455

AC XY:

33068

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.256

AC:

8559

AN:

33478

American (AMR)

AF:

0.0694

AC:

3102

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0804

AC:

2101

AN:

26136

East Asian (EAS)

AF:

0.0704

AC:

2793

AN:

39698

South Asian (SAS)

AF:

0.104

AC:

8954

AN:

86258

European-Finnish (FIN)

AF:

0.0497

AC:

2654

AN:

53420

Middle Eastern (MID)

AF:

0.0364

AC:

210

AN:

5768

European-Non Finnish (NFE)

AF:

0.0299

AC:

33236

AN:

1111990

Other (OTH)

AF:

0.0569

AC:

3439

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

3778

7556

11334

15112

18890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1546

3092

4638

6184

7730

<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:

0.102

AC:

15561

AN:

151978

Hom.:

1503

Cov.:

AF XY:

0.102

AC XY:

7610

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.253

AC:

10469

AN:

41408

American (AMR)

AF:

0.0757

AC:

1155

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0791

AC:

274

AN:

3466

East Asian (EAS)

AF:

0.0619

AC:

319

AN:

5156

South Asian (SAS)

AF:

0.107

AC:

517

AN:

4812

European-Finnish (FIN)

AF:

0.0545

AC:

577

AN:

10584

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0296

AC:

2014

AN:

67972

Other (OTH)

AF:

0.0773

AC:

163

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

619

1238

1858

2477

3096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0279

Hom.:

Bravo

AF:

0.110

Asia WGS

AF:

0.103

AC:

361

AN:

3478

EpiCase

AF:

0.0330

EpiControl

AF:

0.0348

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DLGAP1-related disorder

Benign:1

Jun 04, 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

-0.51

CADD

Benign

3.0

(source)

DANN

Benign

0.51

PhyloP100

-0.19

Mutation Taster

=98/2

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