chrX-70445301-C-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PM2PP3_ModeratePP5_Moderate
The NM_021120.4(DLG3):c.100C>T(p.Gln34Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 24)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
DLG3
NM_021120.4 stop_gained
NM_021120.4 stop_gained
Scores
2
2
1
Clinical Significance
Conservation
PhyloP100: 5.69
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant X-70445301-C-T is Pathogenic according to our data. Variant chrX-70445301-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2577711.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLG3 | NM_021120.4 | c.100C>T | p.Gln34Ter | stop_gained | 1/19 | ENST00000374360.8 | |
DLG3 | XM_006724625.3 | c.100C>T | p.Gln34Ter | stop_gained | 1/20 | ||
DLG3 | XM_011530883.2 | c.100C>T | p.Gln34Ter | stop_gained | 1/19 | ||
DLG3 | XM_006724626.3 | c.100C>T | p.Gln34Ter | stop_gained | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLG3 | ENST00000374360.8 | c.100C>T | p.Gln34Ter | stop_gained | 1/19 | 1 | NM_021120.4 | ||
DLG3 | ENST00000194900.8 | c.100C>T | p.Gln34Ter | stop_gained | 1/21 | 5 | P1 | ||
DLG3 | ENST00000463252.5 | n.166C>T | non_coding_transcript_exon_variant | 1/19 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1051229Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 343215
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1051229
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
343215
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 22, 2023 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.