NM_001985.3:c.687C>G

Variant names:

• chr19-51345292-G-C
• rs200877363
• NM_001985.3:c.687C>G

Variant summary

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

The NM_001985.3(ETFB):​c.687C>G​(p.Asp229Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ETFB NM_001985.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

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=0.08485389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETFB	NM_001985.3	c.687C>G	p.Asp229Glu	missense_variant	Exon 6 of 6	ENST00000309244.9	NP_001976.1
ETFB	NM_001014763.1	c.960C>G	p.Asp320Glu	missense_variant	Exon 5 of 5		NP_001014763.1
ETFB	XM_024451418.2	c.576C>G	p.Asp192Glu	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.687C>G	p.Asp229Glu	missense_variant	Exon 6 of 6	1	NM_001985.3	ENSP00000311930.3
ETFB	ENST00000354232.8	c.960C>G	p.Asp320Glu	missense_variant	Exon 5 of 5	1		ENSP00000346173.3
ETFB	ENST00000596253.1	c.528C>G	p.Asp176Glu	missense_variant	Exon 5 of 5	3		ENSP00000469628.1
ENSG00000267984	ENST00000600974.1	n.78+46G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251470 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135916

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 SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.2
DANN	Benign	0.77
DEOGEN2	Benign	0.045	.;T;.
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.87	D;D;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.61	.;N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.42	N;N;.
REVEL	Benign	0.27
Sift	Benign	1.0	T;T;.
Sift4G	Benign	1.0	T;T;.
Polyphen		0.0010	B;B;.
Vest4		0.17
MutPred		0.21		.;Gain of glycosylation at P231 (P = 0.1014);.;
MVP		0.75
MPC		0.20
ClinPred		0.033	T
GERP RS		2.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.18
gMVP		0.25

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: rs200877363; hg19: chr19-51848546;