1-29194142-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_016011.5(MECR):c.1002C>A(p.Leu334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000724 in 1,613,664 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L334L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (3 hom.)
• Consequence: MECR NM_016011.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0420

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 1-29194142-G-T is Benign according to our data. Variant chr1-29194142-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1559111.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.042 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MECR	NM_016011.5	c.1002C>A	p.Leu334=	synonymous_variant	10/10	ENST00000263702.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECR	ENST00000263702.11	c.1002C>A	p.Leu334=	synonymous_variant	10/10	1	NM_016011.5	P1

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000455 AC: 114 AN: 250594 Hom.: 1 AF XY: 0.000576 AC XY: 78 AN XY: 135464

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000589

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000688

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000758 AC: 1108 AN: 1461334 Hom.: 3 Cov.: 31 AF XY: 0.000779 AC XY: 566 AN XY: 726994

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000313

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000568

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000915

Gnomad4 OTH exome AF: 0.000381

GnomAD4 genome AF: 0.000400 AC: 61 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74502

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000315 Hom.: 0

Bravo AF: 0.000400

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	10
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140504683; hg19: chr1-29520654;