NM_138777.5:c.332C>T

Variant names:

• chr9-122280590-C-T
• rs763250108
• NM_138777.5:c.332C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_138777.5(MRRF):​c.332C>T​(p.Thr111Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T111S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRRF NM_138777.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.79
• Publications: 0 publications found

Genes affected

MRRF (HGNC:7234): (mitochondrial ribosome recycling factor) This gene encodes a ribosome recycling factor, which is a component of the mitochondrial translational machinery. The encoded protein, along with mitochondrial elongation factor 2, functions in ribosomal recycling at the termination of mitochondrial translation by mediating the disassembly of ribosomes from messenger RNA. A pseudogene of this gene has been identified on chromosome X. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRRF	NM_138777.5	c.332C>T	p.Thr111Ile	missense_variant	Exon 3 of 7	ENST00000344641.8	NP_620132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRRF	ENST00000344641.8	c.332C>T	p.Thr111Ile	missense_variant	Exon 3 of 7	2	NM_138777.5	ENSP00000343867.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T;.;.;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T;T;.;T;T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.9	L;.;L;.;L
PhyloP100		6.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D
REVEL	Uncertain	0.44
Sift	Benign	0.086	T;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		0.96	D;.;P;.;P
Vest4		0.95
MutPred		0.74		Gain of catalytic residue at P113 (P = 0.0363);Gain of catalytic residue at P113 (P = 0.0363);Gain of catalytic residue at P113 (P = 0.0363);.;Gain of catalytic residue at P113 (P = 0.0363);
MVP		0.86
MPC		0.31
ClinPred		0.94	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.50
gMVP		0.73
Mutation Taster		=12/88	disease causing

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: rs763250108; hg19: chr9-125042869;