ENST00000354232.8:c.278delC

Variant names:

• chr19-51354360-TG-T
• rs74357706
• ENST00000354232.8:c.278delC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The ENST00000354232.8(ETFB):​c.278delC​(p.Pro93HisfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ETFB ENST00000354232.8 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.08
• Publications: 1 publications found

Genes affected

ETFB (HGNC:3482): (electron transfer flavoprotein subunit beta) This gene encodes electron-transfer-flavoprotein, beta polypeptide, which shuttles electrons between primary flavoprotein dehydrogenases involved in mitochondrial fatty acid and amino acid catabolism and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. The gene deficiencies have been implicated in type II glutaricaciduria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ETFB Gene-Disease associations (from GenCC):

• multiple acyl-CoA dehydrogenase deficiency

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

ENSG00000269403 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354232.8. 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
	ETFB	NM_001985.3	MANE Select	c.58-53delC		intron	N/A	NP_001976.1	P38117-1
	ETFB	NM_001014763.1		c.278delC	p.Pro93HisfsTer21	frameshift	Exon 1 of 5	NP_001014763.1	P38117-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETFB	ENST00000354232.8	TSL:1	c.278delC	p.Pro93HisfsTer21	frameshift	Exon 1 of 5	ENSP00000346173.3	P38117-2
	ETFB	ENST00000309244.9	TSL:1 MANE Select	c.58-53delC		intron	N/A	ENSP00000311930.3	P38117-1
	ENSG00000269403	ENST00000600067.1	TSL:5	n.116-53delC		intron	N/A	ENSP00000469452.1	M0QXX7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs74357706;

hg19: chr19-51857614;