NM_004453.4:c.79C>A

Variant names:

• chr4-158680511-C-A
• NM_004453.4:c.79C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004453.4(ETFDH):​c.79C>A​(p.Pro27Thr) 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. 13/21 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ETFDH NM_004453.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

Genes affected

ETFDH (HGNC:3483): (electron transfer flavoprotein dehydrogenase) This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain. Mutations in this gene are associated with glutaric acidemia. Alternatively spliced transcript variants that encode distinct isoforms have been observed. [provided by RefSeq, Aug 2013]

ACMG classification

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=0.38657182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETFDH	NM_004453.4	c.79C>A	p.Pro27Thr	missense_variant	Exon 2 of 13	ENST00000511912.6	NP_004444.2
ETFDH	NM_001281737.2	c.35-1684C>A		intron_variant	Intron 1 of 11		NP_001268666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETFDH	ENST00000511912.6	c.79C>A	p.Pro27Thr	missense_variant	Exon 2 of 13	1	NM_004453.4	ENSP00000426638.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449904 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 722040

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.090	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.012	D
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.34
MutPred		0.66		Loss of glycosylation at P27 (P = 0.0298);
MVP		0.93
MPC		0.11
ClinPred		0.40	T
GERP RS		3.9
Varity_R		0.079
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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.

Other links and lift over

hg19: chr4-159601663;