dbSNP rs11587343: DLGAP3:p.Tyr747Tyr (chr1-34868849-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_001080418.3(DLGAP3):c.2241C>T(p.Tyr747Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,586,072 control chromosomes in the GnomAD database, including 10 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 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 10 hom. )

Consequence

DLGAP3
NM_001080418.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

2 publications found

Variant links:

Genes affected

DLGAP3 (HGNC:30368): (DLG associated protein 3) Predicted to enable PDZ domain binding activity; molecular adaptor activity; and scaffold protein binding activity. Predicted to be involved in protein-containing complex assembly and regulation of postsynaptic neurotransmitter receptor activity. Predicted to be located in synapse. Predicted to be part of postsynaptic density. Predicted to be active in several cellular components, including cholinergic synapse; glutamatergic synapse; and neuromuscular junction. [provided by Alliance of Genome Resources, Apr 2022]

DLGAP3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP7

Synonymous conserved (PhyloP=-1.1 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3 link	c.2241C>T	p.Tyr747Tyr	synonymous_variant	Exon 9 of 12	ENST00000373347.6	NP_001073887.1	O95886
DLGAP3	XM_011541879.3 link	c.2241C>T	p.Tyr747Tyr	synonymous_variant	Exon 10 of 13		XP_011540181.1	O95886
DLGAP3	XM_047426631.1 link	c.2241C>T	p.Tyr747Tyr	synonymous_variant	Exon 9 of 12		XP_047282587.1
DLGAP3	XM_011541880.3 link	c.750C>T	p.Tyr250Tyr	synonymous_variant	Exon 5 of 8		XP_011540182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6 link	c.2241C>T	p.Tyr747Tyr	synonymous_variant	Exon 9 of 12	5	NM_001080418.3	ENSP00000362444.1		O95886
DLGAP3	ENST00000235180.4 link	c.2241C>T	p.Tyr747Tyr	synonymous_variant	Exon 7 of 10	2		ENSP00000235180.4		O95886

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00368

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00183

AC:

387

AN:

211766

AF XY:

0.00179

show subpopulations

Gnomad AFR exome

AF:

0.000806

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.000112

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000877

Gnomad NFE exome

AF:

0.00369

Gnomad OTH exome

AF:

0.00225

GnomAD4 exome

AF:

0.00305

AC:

4372

AN:

1433780

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

2108

AN XY:

711682

show subpopulations

African (AFR)

AF:

0.000514

AC:

AN:

33106

American (AMR)

AF:

0.000184

AC:

AN:

43432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25542

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39142

South Asian (SAS)

AF:

0.000153

AC:

AN:

84932

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

39374

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00381

AC:

4208

AN:

1103162

Other (OTH)

AF:

0.00184

AC:

109

AN:

59400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

248

496

743

991

1239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<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:

0.00188

AC:

287

AN:

152292

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000673

AC:

AN:

41574

American (AMR)

AF:

0.000196

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00368

AC:

250

AN:

68008

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00204

Hom.:

Bravo

AF:

0.00169

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.44

(source)

DANN

Benign

0.71

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over