3-197085586-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_001366207.1(DLG1):c.1832A>T(p.Lys611Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
DLG1
NM_001366207.1 missense
NM_001366207.1 missense
Scores
10
7
1
Clinical Significance
Conservation
PhyloP100: 4.17
Genes affected
DLG1 (HGNC:2900): (discs large MAGUK scaffold protein 1) This gene encodes a multi-domain scaffolding protein that is required for normal development. This protein may have a role in septate junction formation, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. A multitude of transcript variants deriving from alternative splicing and the use of multiple alternate promoter have been observed, including some splice variants that may be specific to brain and other tissues. An upstream uORF may regulate translation at some splice variants of this gene. [provided by RefSeq, Sep 2018]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.824
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLG1 | NM_001366207.1 | c.1832A>T | p.Lys611Ile | missense_variant | 16/25 | ENST00000667157.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLG1 | ENST00000667157.1 | c.1832A>T | p.Lys611Ile | missense_variant | 16/25 | NM_001366207.1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152062Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251280Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135808
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727198
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
DLG1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 07, 2023 | The DLG1 c.1931A>T variant is predicted to result in the amino acid substitution p.Lys644Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-196812457-T-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;.;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M;.;.;M;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D
Polyphen
D;.;D;.;.;D;.;D;D
Vest4
MutPred
Loss of methylation at K644 (P = 0.0031);.;Loss of methylation at K644 (P = 0.0031);.;.;Loss of methylation at K644 (P = 0.0031);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at