rs749435497

Variant names:

• chr1-29230945-C-G
• rs749435497
• ENST00000883815.1:c.-39G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-29230945-C-G
• chr1-29230945-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000883815.1(MECR):​c.-39G>C variant causes a 5 prime UTR 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 ENST00000883815.1 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: 3.41
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000883815.1. 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.-39G>C		upstream_gene	N/A	NP_057095.4	Q9BV79-1
	MECR	NM_001349715.2		c.-39G>C		upstream_gene	N/A	NP_001336644.1
	MECR	NM_001349716.2		c.-39G>C		upstream_gene	N/A	NP_001336645.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MECR	ENST00000883815.1		c.-39G>C		5_prime_UTR	Exon 1 of 11	ENSP00000553874.1
	MECR	ENST00000263702.11	TSL:1 MANE Select	c.-39G>C		upstream_gene	N/A	ENSP00000263702.6	Q9BV79-1
	MECR	ENST00000944953.1		c.-39G>C		upstream_gene	N/A	ENSP00000615012.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397944 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 691974

African (AFR) AF: 0.00 AC: 0 AN: 30696

American (AMR) AF: 0.00 AC: 0 AN: 33268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23388

East Asian (EAS) AF: 0.00 AC: 0 AN: 37840

South Asian (SAS) AF: 0.00 AC: 0 AN: 80288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3906

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1087486

Other (OTH) AF: 0.00 AC: 0 AN: 57568

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.90
PhyloP100		3.4
PromoterAI		-0.89	Under-expression

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs749435497;

hg19: chr1-29557457;