Variant 12-123233754-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_152269.5(MTRFR):c.-29+223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,298 control chromosomes in the GnomAD database, including 30,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.59 ( 30807 hom., cov: 31)

Exomes 𝑓: 0.80 ( 90 hom. )

Consequence

MTRFR
NM_152269.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.613

Variant links:

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 links:

MPHOSPH9 (HGNC:7215): (M-phase phosphoprotein 9) Located in Golgi apparatus and centriole. Implicated in multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

MPHOSPH9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 12-123233754-C-T is Benign according to our data. Variant chr12-123233754-C-T is described in ClinVar as [Benign]. Clinvar id is 671535.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTRFR	NM_152269.5 linkuse as main transcript	c.-29+223C>T		intron_variant		ENST00000253233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTRFR	ENST00000253233.6 linkuse as main transcript	c.-29+223C>T		intron_variant		1	NM_152269.5	P1	Q9H3J6-1

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89699

AN:

151900

Hom.:

30806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.746

Gnomad AMR

AF:

0.683

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.726

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.749

Gnomad OTH

AF:

0.619

GnomAD4 exome

AF:

0.800

AC:

224

AN:

280

Hom.:

Cov.:

AF XY:

0.807

AC XY:

171

AN XY:

212

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.833

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.772

Gnomad4 OTH exome

AF:

0.900

GnomAD4 genome

AF:

0.590

AC:

89717

AN:

152018

Hom.:

30807

Cov.:

AF XY:

0.595

AC XY:

44214

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.682

Gnomad4 ASJ

AF:

0.645

Gnomad4 EAS

AF:

0.726

Gnomad4 SAS

AF:

0.722

Gnomad4 FIN

AF:

0.751

Gnomad4 NFE

AF:

0.749

Gnomad4 OTH

AF:

0.623

Alfa

AF:

0.657

Hom.:

4343

Bravo

AF:

0.563

Asia WGS

AF:

0.697

AC:

2424

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.8

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over