NM_001985.3:c.728A>C

Variant names:

• chr19-51345251-T-G
• rs398123677
• NM_001985.3:c.728A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001985.3(ETFB):​c.728A>C​(p.Glu243Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ETFB NM_001985.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19923043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETFB	NM_001985.3	c.728A>C	p.Glu243Ala	missense_variant	Exon 6 of 6	ENST00000309244.9	NP_001976.1
ETFB	NM_001014763.1	c.1001A>C	p.Glu334Ala	missense_variant	Exon 5 of 5		NP_001014763.1
ETFB	XM_024451418.2	c.617A>C	p.Glu206Ala	missense_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.728A>C	p.Glu243Ala	missense_variant	Exon 6 of 6	1	NM_001985.3	ENSP00000311930.3
ETFB	ENST00000354232.8	c.1001A>C	p.Glu334Ala	missense_variant	Exon 5 of 5	1		ENSP00000346173.3
ENSG00000267984	ENST00000600974.1	n.78+5T>G		splice_region_variant, intron_variant	Intron 1 of 1	3
ETFB	ENST00000596253.1	c.*34A>C		downstream_gene_variant		3		ENSP00000469628.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74380

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 01, 2012

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.0064	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.36	.;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Benign	0.25
Sift	Benign	0.65	T;T
Sift4G	Benign	0.76	T;T
Polyphen		0.0030	B;B
Vest4		0.30
MutPred		0.37		.;Gain of MoRF binding (P = 0.0281);
MVP		0.91
MPC		0.23
ClinPred		0.55	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.56

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: rs398123677; hg19: chr19-51848505;