chr1-29195193-C-T

Variant names:

• chr1-29195193-C-T
• rs12738007
• NM_016011.5:c.964+748G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016011.5(MECR):​c.964+748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,024 control chromosomes in the GnomAD database, including 9,959 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (9959 hom., cov: 32)
• Consequence: MECR NM_016011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MECR	NM_016011.5	c.964+748G>A		intron_variant	Intron 9 of 9	ENST00000263702.11	NP_057095.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MECR	ENST00000263702.11	c.964+748G>A		intron_variant	Intron 9 of 9	1	NM_016011.5	ENSP00000263702.6

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49336 AN: 151906 Hom.: 9955 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.325 AC: 49352 AN: 152024 Hom.: 9959 Cov.: 32 AF XY: 0.328 AC XY: 24386 AN XY: 74282

African (AFR) AF: 0.105 AC: 4355 AN: 41504

American (AMR) AF: 0.347 AC: 5298 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1394 AN: 3466

East Asian (EAS) AF: 0.0738 AC: 382 AN: 5176

South Asian (SAS) AF: 0.324 AC: 1561 AN: 4816

European-Finnish (FIN) AF: 0.495 AC: 5219 AN: 10538

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30020 AN: 67942

Other (OTH) AF: 0.320 AC: 675 AN: 2112

Alfa AF: 0.388 Hom.: 16075

Bravo AF: 0.298

Asia WGS AF: 0.209 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.68
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12738007; hg19: chr1-29521705;