6-152991220-C-A

Variant names:

• chr6-152991220-C-A
• rs935752801
• NM_019041.7:c.907G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019041.7(MTRF1L):​c.907G>T​(p.Glu303*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000354 in 1,411,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: MTRF1L NM_019041.7 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83
• Publications: 0 publications found

Genes affected

MTRF1L (HGNC:21051): (mitochondrial translation release factor 1 like) The protein encoded by this gene plays a role in mitochondrial translation termination, and is thought to be a release factor that is involved in the dissociation of the complete protein from the final tRNA, the ribosome, and the cognate mRNA. This protein acts upon UAA and UAG stop codons, but has no in vitro activity against UGA, which encodes tryptophan in human mitochondrion, or, the mitochondrial non-cognate stop codons, AGA and AGG. This protein shares sequence similarity to bacterial release factors. Pseudogenes of this gene are found on chromosomes 4, 8, and 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

ENSG00000227627 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019041.7. 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
	MTRF1L	NM_019041.7	MANE Select	c.907G>T	p.Glu303*	stop_gained	Exon 6 of 7	NP_061914.3
	MTRF1L	NM_001301870.2		c.799G>T	p.Glu267*	stop_gained	Exon 6 of 7	NP_001288799.1
	MTRF1L	NM_001301871.2		c.481G>T	p.Glu161*	stop_gained	Exon 6 of 7	NP_001288800.1	Q9UGC7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTRF1L	ENST00000367233.10	TSL:1 MANE Select	c.907G>T	p.Glu303*	stop_gained	Exon 6 of 7	ENSP00000356202.5	Q9UGC7-1
	MTRF1L	ENST00000367231.9	TSL:1	c.806-1125G>T		intron	N/A	ENSP00000356200.5	Q9UGC7-2
	MTRF1L	ENST00000367230.5	TSL:1	c.698-1125G>T		intron	N/A	ENSP00000356199.1	Q9UGC7-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 195590 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000354 AC: 5 AN: 1411388 Hom.: 0 Cov.: 30 AF XY: 0.00000286 AC XY: 2 AN XY: 700200

African (AFR) AF: 0.0000324 AC: 1 AN: 30910

American (AMR) AF: 0.00 AC: 0 AN: 34994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24366

East Asian (EAS) AF: 0.0000261 AC: 1 AN: 38328

South Asian (SAS) AF: 0.00 AC: 0 AN: 77118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4036

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1091564

Other (OTH) AF: 0.0000172 AC: 1 AN: 58168

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		3.8
Vest4		0.26
GERP RS		5.2
Mutation Taster		=18/182	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: rs935752801; hg19: chr6-153312355;