rs17203281
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001321075.3(DLG4):c.1167C>T(p.Ile389Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,368 control chromosomes in the GnomAD database, including 77,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.28 ( 6382 hom., cov: 32)
Exomes 𝑓: 0.31 ( 70993 hom. )
Consequence
DLG4
NM_001321075.3 synonymous
NM_001321075.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.74
Genes affected
DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 17-7196492-G-A is Benign according to our data. Variant chr17-7196492-G-A is described in ClinVar as [Benign]. Clinvar id is 1255506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.74 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DLG4 | NM_001321075.3 | c.1167C>T | p.Ile389Ile | synonymous_variant | 10/20 | ENST00000399506.9 | NP_001308004.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DLG4 | ENST00000399506.9 | c.1167C>T | p.Ile389Ile | synonymous_variant | 10/20 | 2 | NM_001321075.3 | ENSP00000382425.2 | ||
DLG4 | ENST00000648172.8 | c.1296C>T | p.Ile432Ile | synonymous_variant | 12/22 | ENSP00000497806.3 | ||||
DLG4 | ENST00000648896.1 | c.1266C>T | p.Ile422Ile | synonymous_variant | 10/20 | ENSP00000497546.1 | ||||
DLG4 | ENST00000649520.1 | c.987C>T | p.Ile329Ile | synonymous_variant | 9/19 | ENSP00000497647.1 | ||||
DLG4 | ENST00000648263.1 | c.987C>T | p.Ile329Ile | synonymous_variant | 8/14 | ENSP00000498035.1 | ||||
DLG4 | ENST00000491753.2 | n.1296C>T | non_coding_transcript_exon_variant | 12/21 | 2 | ENSP00000467897.2 |
Frequencies
GnomAD3 genomes AF: 0.281 AC: 42701AN: 151992Hom.: 6380 Cov.: 32
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GnomAD3 exomes AF: 0.283 AC: 70531AN: 249188Hom.: 10847 AF XY: 0.286 AC XY: 38690AN XY: 135178
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GnomAD4 exome AF: 0.307 AC: 449018AN: 1461258Hom.: 70993 Cov.: 39 AF XY: 0.306 AC XY: 222099AN XY: 726908
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GnomAD4 genome AF: 0.281 AC: 42707AN: 152110Hom.: 6382 Cov.: 32 AF XY: 0.281 AC XY: 20898AN XY: 74360
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 03, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Intellectual developmental disorder 62 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
DLG4-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 24, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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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