Variant chrX-70452019-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_021120.4(DLG3):c.1138T>C(p.Phe380Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000265 in 1,208,522 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000028 ( 0 hom. 12 hem. )

Consequence

DLG3
NM_021120.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 4.69

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4063073).

BS2

High Hemizygotes in GnomAdExome4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG3	NM_021120.4 linkuse as main transcript	c.1138T>C	p.Phe380Leu	missense_variant	7/19	ENST00000374360.8	NP_066943.2	Q92796-1Q59FY1
DLG3	XM_006724625.3 linkuse as main transcript	c.1138T>C	p.Phe380Leu	missense_variant	7/20		XP_006724688.1
DLG3	XM_011530883.2 linkuse as main transcript	c.1138T>C	p.Phe380Leu	missense_variant	7/19		XP_011529185.1
DLG3	XM_006724626.3 linkuse as main transcript	c.1138T>C	p.Phe380Leu	missense_variant	7/20		XP_006724689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DLG3	ENST00000374360.8 linkuse as main transcript	c.1138T>C	p.Phe380Leu	missense_variant	7/19	1	NM_021120.4	ENSP00000363480.3	Q92796-1
DLG3	ENST00000194900.8 linkuse as main transcript	c.1192T>C	p.Phe398Leu	missense_variant	8/21	5		ENSP00000194900.4	Q5JUW8
DLG3	ENST00000463252.5 linkuse as main transcript	n.1537T>C		non_coding_transcript_exon_variant	6/19	5

Frequencies

GnomAD3 genomes

AF:

0.00000901

AC:

AN:

110947

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33187

show subpopulations

Gnomad AFR

AF:

0.0000329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000219

AC:

AN:

182333

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66833

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000369

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000282

AC:

AN:

1097575

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

362991

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.0000321

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.00000901

AC:

AN:

110947

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33187

show subpopulations

Gnomad4 AFR

AF:

0.0000329

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Intellectual disability, X-linked 90

Uncertain:2

Uncertain significance, criteria provided, single submitter	research	Laboratory of Medical Genetics, University of Torino	Nov 29, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Nov 23, 2021	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 20, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

T;T

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.069

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.24

Sift

Benign

0.34

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0040

.;B

Vest4

0.57

MutPred

0.39

.;Gain of disorder (P = 0.1078);

MVP

0.87

MPC

0.84

ClinPred

0.25

GERP RS

3.9

Varity_R

0.28

gMVP

0.43

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