ENST00000908733.1:c.-29+1157T>G – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000908733.1(MTRFR):c.-29+1157T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

MTRFR
ENST00000908733.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.166

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000908733.1. 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.-166T>G		upstream_gene	N/A	NP_689482.1	Q9H3J6-1
	MTRFR	NM_001194995.1		c.-559T>G		upstream_gene	N/A	NP_001181924.1	Q9H3J6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTRFR	ENST00000908733.1		c.-29+1157T>G	intron	N/A	ENSP00000578792.1
MTRFR	ENST00000918248.1		c.-29+12T>G	intron	N/A	ENSP00000588307.1
MPHOSPH9	ENST00000545406.1	TSL:4	c.-158-2872A>C	intron	N/A	ENSP00000446334.1	F5H1W2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.1

(source)

DANN

Benign

0.71

PhyloP100

-0.17

PromoterAI

-0.0098

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over