rs6145976

Variant names:

• chr17-7219921-T-TGGGCGTGCAGGACGCGGGCACGC
• rs6145976
• ENST00000350303.9:c.-49_-48insGGGCACGCGGGCGTGCAGGACGC

Your query was ambiguous. Multiple possible variants found:

• chr17-7219921-T-TGGGCGTGCAGGACGCGGGCACGC
• chr17-7219921-T-TGGGCGTGCAGGACGC
• chr17-7219921-T-TGGGCGTGCAGGACGCGGGCGTGCAGGACGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000350303.9(ACADVL):​c.-49_-48insGGGCACGCGGGCGTGCAGGACGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 0)
• Consequence: ACADVL ENST00000350303.9 5_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -2.14
• Publications: 6 publications found

Genes affected

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]

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]

DLG4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder 62

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000350303.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	NR_135527.1		n.129_130insGCGTGCCCGCGTCCTGCACGCCC		non_coding_transcript_exon	Exon 1 of 21
	DLG4	NM_001321074.1		c.-1073_-1072insGCGTGCCCGCGTCCTGCACGCCC		5_prime_UTR	Exon 1 of 22	NP_001308003.1
	ACADVL	NM_001270447.2		c.132-186_132-185insGGGCACGCGGGCGTGCAGGACGC		intron	N/A	NP_001257376.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADVL	ENST00000350303.9	TSL:1	c.-49_-48insGGGCACGCGGGCGTGCAGGACGC		5_prime_UTR	Exon 1 of 19	ENSP00000344152.5
	ACADVL	ENST00000322910.9	TSL:2	n.-49_-48insGGGCACGCGGGCGTGCAGGACGC		non_coding_transcript_exon	Exon 1 of 19	ENSP00000325395.5
	ACADVL	ENST00000577191.5	TSL:2	n.29_30insGGGCACGCGGGCGTGCAGGACGC		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 99

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Very long chain acyl-CoA dehydrogenase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs6145976; hg19: chr17-7123240;