17-7217169-G-A

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

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.74
Variant links:
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
DLG4NM_001321075.3 linkuse as main transcriptc.-22C>T 5_prime_UTR_premature_start_codon_gain_variant 1/20 ENST00000399506.9 NP_001308004.1 P78352-1
DLG4NM_001321075.3 linkuse as main transcriptc.-22C>T 5_prime_UTR_variant 1/20 ENST00000399506.9 NP_001308004.1 P78352-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DLG4ENST00000399506.9 linkuse as main transcriptc.-22C>T 5_prime_UTR_premature_start_codon_gain_variant 1/202 NM_001321075.3 ENSP00000382425.2 P78352-1
DLG4ENST00000647975.1 linkuse as main transcriptc.-22C>T 5_prime_UTR_premature_start_codon_gain_variant 1/7 ENSP00000497912.1 A0A3B3ITI9
DLG4ENST00000399506.9 linkuse as main transcriptc.-22C>T 5_prime_UTR_variant 1/202 NM_001321075.3 ENSP00000382425.2 P78352-1
DLG4ENST00000647975.1 linkuse as main transcriptc.-22C>T 5_prime_UTR_variant 1/7 ENSP00000497912.1 A0A3B3ITI9
DLG4ENST00000648172.8 linkuse as main transcriptc.159+1072C>T intron_variant ENSP00000497806.3 P78352-2
DLG4ENST00000491753.2 linkuse as main transcriptn.159+1072C>T intron_variant 2 ENSP00000467897.2 B7Z3U2

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151622
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000283
AC:
32
AN:
1132542
Hom.:
0
Cov.:
32
AF XY:
0.0000332
AC XY:
18
AN XY:
542172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000369
Gnomad4 SAS exome
AF:
0.0000740
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.0000220
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151622
Hom.:
0
Cov.:
29
AF XY:
0.0000135
AC XY:
1
AN XY:
74024
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 providedclinical testingPreventionGenetics, part of Exact SciencesJul 10, 2024This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
CADD
Benign
16
DANN
Benign
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1210786746; hg19: chr17-7120488; API