Variant rs371545673 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2

The NM_021120.4(DLG3):c.1388C>T(p.Ala463Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,207,737 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.0000082 ( 0 hom. 2 hem. )

Consequence

DLG3
NM_021120.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.54

Variant links:

Genes affected

DLG3 (HGNC:2902): (discs large MAGUK scaffold protein 3) This gene encodes a member of the membrane-associated guanylate kinase protein family. The encoded protein may play a role in clustering of NMDA receptors at excitatory synapses. It may also negatively regulate cell proliferation through interaction with the C-terminal region of the adenomatosis polyposis coli tumor suppressor protein. Mutations in this gene have been associated with X-linked cognitive disability. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

DLG3 links:

DLG3 (HGNC:):

DLG3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3834181).

BP6

Variant X-70454299-C-T is Benign according to our data. Variant chrX-70454299-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 210849.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00017 (19/111789) while in subpopulation AFR AF= 0.000456 (14/30716). AF 95% confidence interval is 0.000275. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG3	NM_021120.4 linkuse as main transcript	c.1388C>T	p.Ala463Val	missense_variant	9/19	ENST00000374360.8	NP_066943.2	Q92796-1Q59FY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG3	ENST00000374360.8 linkuse as main transcript	c.1388C>T	p.Ala463Val	missense_variant	9/19	1	NM_021120.4	ENSP00000363480.3		Q92796-1

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

111789

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33985

show subpopulations

Gnomad AFR

AF:

0.000456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000220

AC:

AN:

181912

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66386

show subpopulations

Gnomad AFR exome

AF:

0.000306

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1095948

Hom.:

Cov.:

AF XY:

0.00000554

AC XY:

AN XY:

361332

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000170

AC:

AN:

111789

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33985

show subpopulations

Gnomad4 AFR

AF:

0.000456

Gnomad4 AMR

AF:

0.000379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 20, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

T;T;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.7

.;N;.

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.045

.;B;.

Vest4

0.81

MVP

0.87

MPC

1.6

ClinPred

0.15

GERP RS

4.9

Varity_R

0.36

gMVP

0.50

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