NM_016011.5:c.1054G>C

Variant names:

• chr1-29194090-C-G
• rs763007974
• NM_016011.5:c.1054G>C

Variant summary

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

The NM_016011.5(MECR):​c.1054G>C​(p.Asp352His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D352E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MECR NM_016011.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51

Genes affected

MECR (HGNC:19691): (mitochondrial trans-2-enoyl-CoA reductase) The protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis. Defects in this gene are a cause of childhood-onset dystonia and optic atrophy. [provided by RefSeq, Mar 2017]

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=0.23710984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECR	NM_016011.5	c.1054G>C	p.Asp352His	missense_variant	Exon 10 of 10	ENST00000263702.11	NP_057095.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MECR	ENST00000263702.11	c.1054G>C	p.Asp352His	missense_variant	Exon 10 of 10	1	NM_016011.5	ENSP00000263702.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	.;M
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.17
Sift	Benign	0.046	D;D
Sift4G	Uncertain	0.037	D;T
Polyphen		0.12	.;B
Vest4		0.17
MutPred		0.39		.;Loss of phosphorylation at Y353 (P = 0.1147);
MVP		0.27
MPC		0.13
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.59
gMVP		0.78

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: rs763007974; hg19: chr1-29520602;