rs11532322

Variant names:

• chr12-123246876-A-G
• rs11532322
• NM_152269.5:c.-28-6771A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-123246876-A-G
• chr12-123246876-A-T

Variant summary

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

The NM_152269.5(MTRFR):​c.-28-6771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,438 control chromosomes in the GnomAD database, including 30,590 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 0.59 (30590 hom., cov: 28)
• Consequence: MTRFR NM_152269.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 28 publications found

Genes affected

MTRFR (HGNC:26784): (mitochondrial translation release factor in rescue) This nuclear gene encodes a mitochondrial matrix protein that appears to contribute to peptide chain termination in the mitochondrial translation machinery. Two different 1 bp deletions (resulting in the same premature stop codon)result in decreased mitochondrial translation, decreased levels of oxidative phosphorylation complexes and encepthalomyopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

MTRFR Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina, ClinGen
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152269.5. 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
	MTRFR	NM_152269.5	MANE Select	c.-28-6771A>G		intron	N/A	NP_689482.1	Q9H3J6-1
	MTRFR	NM_001143905.2		c.-28-6771A>G		intron	N/A	NP_001137377.1	Q9H3J6-1
	MTRFR	NM_001194995.1		c.-28-6771A>G		intron	N/A	NP_001181924.1	Q9H3J6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTRFR	ENST00000253233.6	TSL:1 MANE Select	c.-28-6771A>G		intron	N/A	ENSP00000253233.1	Q9H3J6-1
	MTRFR	ENST00000366329.7	TSL:2	c.-28-6771A>G		intron	N/A	ENSP00000390647.1	Q9H3J6-1
	MTRFR	ENST00000536130.2	TSL:3	c.-28-6771A>G		intron	N/A	ENSP00000443072.2	Q9H3J6-1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89075 AN: 151322 Hom.: 30590 Cov.: 28

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.574

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.588 AC: 89087 AN: 151438 Hom.: 30590 Cov.: 28 AF XY: 0.593 AC XY: 43862 AN XY: 73978

African (AFR) AF: 0.208 AC: 8583 AN: 41230

American (AMR) AF: 0.673 AC: 10254 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2238 AN: 3466

East Asian (EAS) AF: 0.741 AC: 3809 AN: 5140

South Asian (SAS) AF: 0.724 AC: 3474 AN: 4796

European-Finnish (FIN) AF: 0.753 AC: 7858 AN: 10440

Middle Eastern (MID) AF: 0.576 AC: 167 AN: 290

European-Non Finnish (NFE) AF: 0.748 AC: 50730 AN: 67838

Other (OTH) AF: 0.618 AC: 1302 AN: 2108

Alfa AF: 0.554 Hom.: 2056

Bravo AF: 0.561

Asia WGS AF: 0.702 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.0
DANN	Benign	0.21
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11532322; hg19: chr12-123731423;