Variant 1-34905251-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001080418.3(DLGAP3):c.133C>A(p.Pro45Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,592,980 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P45H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 2 hom. )

Consequence

DLGAP3
NM_001080418.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076347888).

BP6

Variant 1-34905251-G-T is Benign according to our data. Variant chr1-34905251-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 722226.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DLGAP3	NM_001080418.3 linkuse as main transcript	c.133C>A	p.Pro45Thr	missense_variant	3/12	ENST00000373347.6
DLGAP3	XM_011541879.3 linkuse as main transcript	c.133C>A	p.Pro45Thr	missense_variant	4/13
DLGAP3	XM_047426631.1 linkuse as main transcript	c.133C>A	p.Pro45Thr	missense_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DLGAP3	ENST00000373347.6 linkuse as main transcript	c.133C>A	p.Pro45Thr	missense_variant	3/12	5	NM_001080418.3	P1
DLGAP3	ENST00000235180.4 linkuse as main transcript	c.133C>A	p.Pro45Thr	missense_variant	1/10	2		P1
DLGAP3	ENST00000495979.1 linkuse as main transcript	n.388C>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00445

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000313

AC:

AN:

204670

Hom.:

AF XY:

0.000351

AC XY:

AN XY:

111250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000656

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00376

Gnomad SAS exome

AF:

0.0000381

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000109

AC:

157

AN:

1440734

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

714466

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000481

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00295

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000655

GnomAD4 genome

AF:

0.000184

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00446

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Bravo

AF:

0.000223

ExAC

AF:

0.000233

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.0024

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.74

T;.

M_CAP

Benign

0.0049

MetaRNN

Benign

0.0076

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.92

N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.083

Sift

Benign

0.23

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.075

B;B

Vest4

0.43

MutPred

0.29

Gain of phosphorylation at P45 (P = 0.0573);Gain of phosphorylation at P45 (P = 0.0573);

MVP

0.20

MPC

0.88

ClinPred

0.029

GERP RS

4.5

Varity_R

0.18

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over