Variant X-70445350-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021120.4(DLG3):c.149G>C(p.Gly50Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000111 in 1,171,691 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000011 ( 0 hom. 4 hem. )

Consequence

DLG3
NM_021120.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

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:

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=0.19466794).

BS2

High Hemizygotes in GnomAdExome4 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.149G>C	p.Gly50Ala	missense_variant	1/19	ENST00000374360.8	NP_066943.2	Q92796-1Q59FY1
DLG3	XM_006724625.3 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	1/20		XP_006724688.1
DLG3	XM_011530883.2 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	1/19		XP_011529185.1
DLG3	XM_006724626.3 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	1/20		XP_006724689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DLG3	ENST00000374360.8 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	1/19	1	NM_021120.4	ENSP00000363480.3	Q92796-1
DLG3	ENST00000194900.8 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	1/21	5		ENSP00000194900.4	Q5JUW8
DLG3	ENST00000463252.5 linkuse as main transcript	n.215G>C		non_coding_transcript_exon_variant	1/19	5

Frequencies

GnomAD3 genomes

AF:

0.00000882

AC:

AN:

113386

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35526

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000906

AC:

AN:

110349

Hom.:

AF XY:

0.00

AC XY:

AN XY:

36611

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000484

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:

0.0000113

AC:

AN:

1058305

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

344801

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000340

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:

0.0000134

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000882

AC:

AN:

113386

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35526

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2022

The c.149G>C (p.G50A) alteration is located in exon 1 (coding exon 1) of the DLG3 gene. This alteration results from a G to C substitution at nucleotide position 149, causing the glycine (G) at amino acid position 50 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.043

T;T

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.080

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.12

Sift

Benign

0.18

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0050

.;B

Vest4

0.14

MutPred

0.47

Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);

MVP

0.47

MPC

1.8

ClinPred

0.16

GERP RS

3.7

Varity_R

0.13

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