NM_001321075.3:c.-22C>T

Variant names:

• chr17-7217169-G-A
• rs1210786746
• NM_001321075.3:c.-22C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

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
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

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]

ACADVL Gene-Disease associations (from GenCC):

• very long chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 3357092.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAdExome4 at 32 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321075.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	NM_001321075.3	MANE Select	c.-22C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	NP_001308004.1	P78352-1
	DLG4	NM_001321075.3	MANE Select	c.-22C>T		5_prime_UTR	Exon 1 of 20	NP_001308004.1	P78352-1
	DLG4	NM_001365.5	MANE Plus Clinical	c.159+1072C>T		intron	N/A	NP_001356.1	P78352-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	ENST00000399506.9	TSL:2 MANE Select	c.-22C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000382425.2	P78352-1
	DLG4	ENST00000485100.5	TSL:1	c.-22C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000460625.1	O14909
	DLG4	ENST00000647975.1		c.-22C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000497912.1	A0A3B3ITI9

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151622 Hom.: 0 Cov.: 29

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

GnomAD2 exomes AF: 0.00 AC: 0 AN: 25678 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome 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

African (AFR) AF: 0.00 AC: 0 AN: 23348

American (AMR) AF: 0.00 AC: 0 AN: 9238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14994

East Asian (EAS) AF: 0.0000369 AC: 1 AN: 27108

South Asian (SAS) AF: 0.0000740 AC: 2 AN: 27018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3610

European-Non Finnish (NFE) AF: 0.0000297 AC: 28 AN: 943886

Other (OTH) AF: 0.0000220 AC: 1 AN: 45364

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151622 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 74024

African (AFR) AF: 0.00 AC: 0 AN: 41274

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5058

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67870

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ACADVL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		1.7
PromoterAI		-0.052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=294/6	polymorphism

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

Other links and lift over

dbSNP: rs1210786746; hg19: chr17-7120488;