17-7217754-C-A

Variant names:

• chr17-7217754-C-A
• ENST00000648172.8:c.159+487G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001270447.2(ACADVL):​c.67C>A​(p.Gln23Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ACADVL NM_001270447.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06180513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.-607G>T		upstream_gene_variant		ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000648172.8	c.159+487G>T		intron_variant	Intron 3 of 21			ENSP00000497806.3
DLG4	ENST00000491753.2	n.159+487G>T		intron_variant	Intron 3 of 20	2		ENSP00000467897.2
DLG4	ENST00000399506.9	c.-607G>T		upstream_gene_variant		2	NM_001321075.3	ENSP00000382425.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383176 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 682508

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.78
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.32	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.062	T
MetaSVM	Uncertain	0.021	D
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Vest4		0.12
MutPred		0.16		Gain of ubiquitination at Q23 (P = 0.0276);
MVP		0.51
MPC		0.25
ClinPred		0.055	T
GERP RS		-2.2
gMVP		0.46

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7121073;