17-7218621-C-T
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001365.5(DLG4):c.38G>A(p.Trp13*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
DLG4
NM_001365.5 stop_gained
NM_001365.5 stop_gained
Scores
3
2
2
Clinical Significance
Conservation
PhyloP100: 2.24
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]
ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 30 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-7218621-C-T is Pathogenic according to our data. Variant chr17-7218621-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 996785.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DLG4 | NM_001365.5 | c.38G>A | p.Trp13* | stop_gained | 2/22 | NP_001356.1 | ||
DLG4 | NM_001321074.1 | c.38G>A | p.Trp13* | stop_gained | 2/22 | NP_001308003.1 | ||
ACADVL | NM_001270447.2 | c.131+803C>T | intron_variant | NP_001257376.1 | ||||
DLG4 | NR_135527.1 | n.1239G>A | non_coding_transcript_exon_variant | 2/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DLG4 | ENST00000648172.8 | c.38G>A | p.Trp13* | stop_gained | 2/22 | ENSP00000497806.3 | ||||
DLG4 | ENST00000399510.8 | c.38G>A | p.Trp13* | stop_gained | 2/22 | 1 | ENSP00000382428.3 | |||
DLG4 | ENST00000491753.2 | n.38G>A | non_coding_transcript_exon_variant | 2/21 | 2 | ENSP00000467897.2 | ||||
ACADVL | ENST00000543245.6 | c.131+803C>T | intron_variant | 2 | ENSP00000438689.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Feb 01, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
Vest4
0.77
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at