Variant chr12-123253386-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152269.5(MTRFR):c.-28-261G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 398,792 control chromosomes in the GnomAD database, including 1,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 645 hom., cov: 30)

Exomes 𝑓: 0.085 ( 1282 hom. )

Consequence

MTRFR
NM_152269.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.132

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:

CDK2AP1 (HGNC:14002): (cyclin dependent kinase 2 associated protein 1) The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. This protein was found to also interact with DNA polymerase alpha/primase and mediate the phosphorylation of the large p180 subunit, which suggests a regulatory role in DNA replication during the S-phase of the cell cycle. This protein also forms a core subunit of the nucleosome remodeling and histone deacetylation (NURD) complex that epigenetically regulates embryonic stem cell differentiation. This gene thus plays a role in both cell-cycle and epigenetic regulation. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]

CDK2AP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 12-123253386-G-T is Benign according to our data. Variant chr12-123253386-G-T is described in ClinVar as [Benign]. Clinvar id is 680559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTRFR	NM_152269.5 link	c.-28-261G>T		intron_variant	Intron 1 of 2	ENST00000253233.6	NP_689482.1	Q9H3J6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTRFR	ENST00000253233.6 link	c.-28-261G>T		intron_variant	Intron 1 of 2	1	NM_152269.5	ENSP00000253233.1		Q9H3J6-1

Frequencies

GnomAD3 genomes

AF:

0.0734

AC:

11125

AN:

151608

Hom.:

645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.0399

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.000969

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.0495

GnomAD4 exome

AF:

0.0848

AC:

20961

AN:

247066

Hom.:

1282

Cov.:

AF XY:

0.0777

AC XY:

10388

AN XY:

133648

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.0312

Gnomad4 ASJ exome

AF:

0.0383

Gnomad4 EAS exome

AF:

0.000905

Gnomad4 SAS exome

AF:

0.0250

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.0813

GnomAD4 genome

AF:

0.0733

AC:

11127

AN:

151726

Hom.:

645

Cov.:

AF XY:

0.0709

AC XY:

5255

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.0399

Gnomad4 ASJ

AF:

0.0329

Gnomad4 EAS

AF:

0.000971

Gnomad4 SAS

AF:

0.0221

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.0490

Alfa

AF:

0.0677

Hom.:

104

Bravo

AF:

0.0634

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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

-0.69

CADD

Benign

3.3

DANN

Benign

0.65

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

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