17-7219921-T-TGGGCGTGCAGGACGCGGGCGTGCAGGACGC

Variant names:

• chr17-7219921-T-TGGGCGTGCAGGACGCGGGCGTGCAGGACGC
• rs6145976
• ENST00000350303.9:c.-49_-48insGGGCGTGCAGGACGCGGGCGTGCAGGACGC

Variant summary

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

The ENST00000322910.9(ACADVL):​n.-49_-48insGGGCGTGCAGGACGCGGGCGTGCAGGACGC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,555,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: ACADVL ENST00000322910.9 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• 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: ENST00000322910.9. 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_130insGCGTCCTGCACGCCCGCGTCCTGCACGCCC		non_coding_transcript_exon	Exon 1 of 21
	DLG4	NM_001321074.1		c.-1073_-1072insGCGTCCTGCACGCCCGCGTCCTGCACGCCC		5_prime_UTR	Exon 1 of 22	NP_001308003.1
	ACADVL	NM_001270447.2		c.132-186_132-185insGGGCGTGCAGGACGCGGGCGTGCAGGACGC		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_-48insGGGCGTGCAGGACGCGGGCGTGCAGGACGC		5_prime_UTR	Exon 1 of 19	ENSP00000344152.5
	ACADVL	ENST00000322910.9	TSL:2	n.-49_-48insGGGCGTGCAGGACGCGGGCGTGCAGGACGC		non_coding_transcript_exon	Exon 1 of 19	ENSP00000325395.5
	ACADVL	ENST00000577191.5	TSL:2	n.29_30insGGGCGTGCAGGACGCGGGCGTGCAGGACGC		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151688 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000420 AC: 59 AN: 1403608 Hom.: 0 Cov.: 99 AF XY: 0.0000533 AC XY: 37 AN XY: 693858

African (AFR) AF: 0.00 AC: 0 AN: 33032

American (AMR) AF: 0.0000824 AC: 3 AN: 36390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25250

East Asian (EAS) AF: 0.000342 AC: 13 AN: 38032

South Asian (SAS) AF: 0.000361 AC: 29 AN: 80326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38350

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5696

European-Non Finnish (NFE) AF: 0.0000101 AC: 11 AN: 1087892

Other (OTH) AF: 0.0000341 AC: 2 AN: 58640

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151808 Hom.: 0 Cov.: 0 AF XY: 0.0000674 AC XY: 5 AN XY: 74214

African (AFR) AF: 0.0000241 AC: 1 AN: 41486

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5120

South Asian (SAS) AF: 0.000624 AC: 3 AN: 4808

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67796

Other (OTH) AF: 0.00 AC: 0 AN: 2104

ClinVar

Not reported in ClinVar

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;