X-70445224-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021120.4(DLG3):​c.23G>A​(p.Cys8Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

DLG3
NM_021120.4 missense

Scores

5
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.64
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DLG3NM_021120.4 linkc.23G>A p.Cys8Tyr missense_variant 1/19 ENST00000374360.8 NP_066943.2 Q92796-1Q59FY1
DLG3XM_006724625.3 linkc.23G>A p.Cys8Tyr missense_variant 1/20 XP_006724688.1
DLG3XM_011530883.2 linkc.23G>A p.Cys8Tyr missense_variant 1/19 XP_011529185.1
DLG3XM_006724626.3 linkc.23G>A p.Cys8Tyr missense_variant 1/20 XP_006724689.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DLG3ENST00000374360.8 linkc.23G>A p.Cys8Tyr missense_variant 1/191 NM_021120.4 ENSP00000363480.3 Q92796-1
DLG3ENST00000194900.8 linkc.23G>A p.Cys8Tyr missense_variant 1/215 ENSP00000194900.4 Q5JUW8
DLG3ENST00000463252.5 linkn.89G>A non_coding_transcript_exon_variant 1/195

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1048884
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
342186
Gnomad4 AFR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxFeb 13, 2024In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.015
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.083
T;T
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Pathogenic
0.32
D
MetaRNN
Uncertain
0.62
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
.;N
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.79
N;N
REVEL
Benign
0.29
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.98
.;D
Vest4
0.65
MutPred
0.60
Loss of ubiquitination at K9 (P = 0.065);Loss of ubiquitination at K9 (P = 0.065);
MVP
0.68
MPC
1.2
ClinPred
0.83
D
GERP RS
4.1
Varity_R
0.87
gMVP
0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-69665074; API