chr19-51354360-TG-T

Position:

• chr19-51354360-TG-T

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PVS1 PM2 BP6

The ENST00000354232.8(ETFB):​c.278del​(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. Variant has been reported in Lovd as Benign (no stars). 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

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 9 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
• BP6: Variant 19-51354360-TG-T is Benign according to our data. Variant chr19-51354360-TG-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETFB	NM_001985.3	c.58-53del		intron_variant		ENST00000309244.9	NP_001976.1
ETFB	NM_001014763.1	c.278del	p.Pro93HisfsTer21	frameshift_variant	1/5		NP_001014763.1
ETFB	XM_024451418.2	c.-54-53del		intron_variant			XP_024307186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETFB	ENST00000354232.8	c.278del	p.Pro93HisfsTer21	frameshift_variant	1/5	1		ENSP00000346173
ETFB	ENST00000309244.9	c.58-53del		intron_variant		1	NM_001985.3	ENSP00000311930	P1
ETFB	ENST00000596253.1	c.58-53del		intron_variant		3		ENSP00000469628
ETFB	ENST00000593992.1	n.81-53del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs74357706; hg19: chr19-51857614;