X-70445292-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_021120.4(DLG3):c.91G>A(p.Gly31Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000271 in 1,164,184 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 96 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 0.00014 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.00029 ( 0 hom. 94 hem. )

Consequence

DLG3
NM_021120.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14971825).

BP6

Variant X-70445292-G-A is Benign according to our data. Variant chrX-70445292-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2346213.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG3	NM_021120.4 link	c.91G>A	p.Gly31Ser	missense_variant	Exon 1 of 19	ENST00000374360.8	NP_066943.2	Q92796-1Q59FY1
DLG3	XM_006724625.3 link	c.91G>A	p.Gly31Ser	missense_variant	Exon 1 of 20		XP_006724688.1
DLG3	XM_011530883.2 link	c.91G>A	p.Gly31Ser	missense_variant	Exon 1 of 19		XP_011529185.1
DLG3	XM_006724626.3 link	c.91G>A	p.Gly31Ser	missense_variant	Exon 1 of 20		XP_006724689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLG3	ENST00000374360.8 link	c.91G>A	p.Gly31Ser	missense_variant	Exon 1 of 19	1	NM_021120.4	ENSP00000363480.3	Q92796-1
DLG3	ENST00000194900.8 link	c.91G>A	p.Gly31Ser	missense_variant	Exon 1 of 21	5		ENSP00000194900.4	Q5JUW8
DLG3	ENST00000463252.5 link	n.157G>A		non_coding_transcript_exon_variant	Exon 1 of 19	5

Frequencies

GnomAD3 genomes

AF:

0.000141

AC:

AN:

113351

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

35491

show subpopulations

Gnomad AFR

AF:

0.0000319

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:

0.000263

Gnomad OTH

AF:

0.000651

GnomAD3 exomes

AF:

0.000128

AC:

AN:

101387

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

36221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000516

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:

0.000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000285

AC:

300

AN:

1050833

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

AN XY:

343209

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000714

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:

0.000360

Gnomad4 OTH exome

AF:

0.0000676

GnomAD4 genome

AF:

0.000141

AC:

AN:

113351

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

35491

show subpopulations

Gnomad4 AFR

AF:

0.0000319

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:

0.000263

Gnomad4 OTH

AF:

0.000651

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000775

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Oct 29, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

T;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.28

N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.23

T;D

Polyphen

1.0

.;D

Vest4

0.27

MVP

0.73

MPC

0.71

ClinPred

0.25

GERP RS

3.8

Varity_R

0.38

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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