17-7217169-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001321075.3(DLG4):c.-22C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,284,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
DLG4
NM_001321075.3 5_prime_UTR_premature_start_codon_gain
NM_001321075.3 5_prime_UTR_premature_start_codon_gain
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.74
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]
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 Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 17-7217169-G-A is Benign according to our data. Variant chr17-7217169-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3357092.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAdExome4 at 32 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DLG4 | NM_001321075.3 | c.-22C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/20 | ENST00000399506.9 | NP_001308004.1 | ||
DLG4 | NM_001321075.3 | c.-22C>T | 5_prime_UTR_variant | 1/20 | ENST00000399506.9 | NP_001308004.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DLG4 | ENST00000399506.9 | c.-22C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/20 | 2 | NM_001321075.3 | ENSP00000382425.2 | |||
DLG4 | ENST00000647975.1 | c.-22C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/7 | ENSP00000497912.1 | |||||
DLG4 | ENST00000399506.9 | c.-22C>T | 5_prime_UTR_variant | 1/20 | 2 | NM_001321075.3 | ENSP00000382425.2 | |||
DLG4 | ENST00000647975.1 | c.-22C>T | 5_prime_UTR_variant | 1/7 | ENSP00000497912.1 | |||||
DLG4 | ENST00000648172.8 | c.159+1072C>T | intron_variant | ENSP00000497806.3 | ||||||
DLG4 | ENST00000491753.2 | n.159+1072C>T | intron_variant | 2 | ENSP00000467897.2 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151622Hom.: 0 Cov.: 29
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GnomAD4 exome AF: 0.0000283 AC: 32AN: 1132542Hom.: 0 Cov.: 32 AF XY: 0.0000332 AC XY: 18AN XY: 542172
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GnomAD4 genome AF: 0.00000660 AC: 1AN: 151622Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1AN XY: 74024
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
ACADVL-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 10, 2024 | This variant is classified as likely 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
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at