Genetic Variant NM_001985.3:c.670G>A (chr19-51345309-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001985.3(ETFB):c.670G>A(p.Val224Met) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ETFB
NM_001985.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

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 links:

ENSG00000267984 (HGNC:):

ENSG00000267984 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3059234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETFB	NM_001985.3 link	c.670G>A	p.Val224Met	missense_variant	Exon 6 of 6	ENST00000309244.9	NP_001976.1	P38117-1
ETFB	NM_001014763.1 link	c.943G>A	p.Val315Met	missense_variant	Exon 5 of 5		NP_001014763.1	P38117-2
ETFB	XM_024451418.2 link	c.559G>A	p.Val187Met	missense_variant	Exon 6 of 6		XP_024307186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ETFB	ENST00000309244.9 link	c.670G>A	p.Val224Met	missense_variant	Exon 6 of 6	1	NM_001985.3	ENSP00000311930.3	P38117-1
ETFB	ENST00000354232.8 link	c.943G>A	p.Val315Met	missense_variant	Exon 5 of 5	1		ENSP00000346173.3	P38117-2
ETFB	ENST00000596253.1 link	c.511G>A	p.Val171Met	missense_variant	Exon 5 of 5	3		ENSP00000469628.1	M0QY67
ENSG00000267984	ENST00000600974.1 link	n.78+63C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.670G>A (p.V224M) alteration is located in exon 6 (coding exon 6) of the ETFB gene. This alteration results from a G to A substitution at nucleotide position 670, causing the valine (V) at amino acid position 224 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

.;T;.

Eigen

Benign

-0.072

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Uncertain

0.57

MutationAssessor

Uncertain

2.8

.;M;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.9

N;N;.

REVEL

Uncertain

0.32

Sift

Uncertain

0.0050

D;D;.

Sift4G

Uncertain

0.0050

D;D;.

Polyphen

0.94

P;B;.

Vest4

0.43

MutPred

0.35

.;Loss of ubiquitination at K221 (P = 0.0609);.;

MVP

0.90

MPC

0.69

ClinPred

0.95

GERP RS

3.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.30

gMVP

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over