dbSNP rs749435497: MECR:c.-39G>C (chr1-29230945-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016011.5(MECR):c.-39G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

MECR
NM_016011.5 upstream_gene

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1O:1

Conservation

PhyloP100: 3.41

Publications

0 publications found

Variant links:

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

MECR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECR	NM_016011.5 link	c.-39G>C		upstream_gene_variant		ENST00000263702.11	NP_057095.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MECR	ENST00000263702.11 link	c.-39G>C		upstream_gene_variant		1	NM_016011.5	ENSP00000263702.6		Q9BV79-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1397944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30696

American (AMR)

AF:

0.00

AC:

AN:

33268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23388

East Asian (EAS)

AF:

0.00

AC:

AN:

37840

South Asian (SAS)

AF:

0.00

AC:

AN:

80288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3906

European-Non Finnish (NFE)

AF:

9.20e-7

AC:

AN:

1087486

Other (OTH)

AF:

0.00

AC:

AN:

57568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities

Uncertain:1Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpretted as Uncertain Significance and reported most recently on 01-16-2018 by Lab or GTR ID 505801. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Jan 16, 2018

Undiagnosed Diseases Network, NIH

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Compound heterozygous variants, c.830+2dupT and c.-39G>C, were detected in this individual. The c.830+2dupT variant disrupts the splice donor consensus and has previously been reported as disease causing [PMID 27817865]. The c.-39G>C variant lies in the 5 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

3.4

PromoterAI

-0.89

Under-expression

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over