19-51345289-C-G

Variant names:

• chr19-51345289-C-G
• rs765255418
• NM_001985.3:c.690G>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001985.3(ETFB):​c.690G>C​(p.Pro230Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 32)
• Consequence: ETFB NM_001985.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.85

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]

ENSG00000267984 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-3.85 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETFB	NM_001985.3	c.690G>C	p.Pro230Pro	synonymous_variant	Exon 6 of 6	ENST00000309244.9	NP_001976.1
ETFB	NM_001014763.1	c.963G>C	p.Pro321Pro	synonymous_variant	Exon 5 of 5		NP_001014763.1
ETFB	XM_024451418.2	c.579G>C	p.Pro193Pro	synonymous_variant	Exon 6 of 6		XP_024307186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETFB	ENST00000309244.9	c.690G>C	p.Pro230Pro	synonymous_variant	Exon 6 of 6	1	NM_001985.3	ENSP00000311930.3
ETFB	ENST00000354232.8	c.963G>C	p.Pro321Pro	synonymous_variant	Exon 5 of 5	1		ENSP00000346173.3
ETFB	ENST00000596253.1	c.531G>C	p.Pro177Pro	synonymous_variant	Exon 5 of 5	3		ENSP00000469628.1
ENSG00000267984	ENST00000600974.1	n.78+43C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.10
DANN	Benign	0.75

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: rs765255418; hg19: chr19-51848543;