chr1-29194167-TC-AA

Variant names:

• chr1-29194167-TC-AA
• NM_016011.5:c.976_977delGAinsTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016011.5(MECR):​c.976_977delGAinsTT​(p.Glu326Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.00000411 in 1 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: GnomAD MNV: 𝑓 0.0000041 Genomes: not found (cov: 32)
• Consequence: MECR NM_016011.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03
• Publications: 0 publications found

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]

MECR Gene-Disease associations (from GenCC):

• dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016011.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MECR	NM_016011.5	MANE Select	c.976_977delGAinsTT	p.Glu326Leu	missense	N/A	NP_057095.4	Q9BV79-1
	MECR	NM_001349715.2		c.1081_1082delGAinsTT	p.Glu361Leu	missense	N/A	NP_001336644.1
	MECR	NM_001349716.2		c.1060_1061delGAinsTT	p.Glu354Leu	missense	N/A	NP_001336645.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MECR	ENST00000263702.11	TSL:1 MANE Select	c.976_977delGAinsTT	p.Glu326Leu	missense	N/A	ENSP00000263702.6	Q9BV79-1
	MECR	ENST00000883815.1		c.1051_1052delGAinsTT	p.Glu351Leu	missense	N/A	ENSP00000553874.1
	MECR	ENST00000944953.1		c.1018_1019delGAinsTT	p.Glu340Leu	missense	N/A	ENSP00000615012.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

GnomAD MNV AF: 0.00000411 AC: 1 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-29520679;