chr6-152994551-T-C

Variant names:

• chr6-152994551-T-C
• NM_019041.7:c.649A>G

Variant summary

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

The NM_019041.7(MTRF1L):​c.649A>G​(p.Ser217Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MTRF1L NM_019041.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.48
• 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]

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.649A>G	p.Ser217Gly	missense	Exon 4 of 7	NP_061914.3
	MTRF1L	NM_001301870.2		c.541A>G	p.Ser181Gly	missense	Exon 4 of 7	NP_001288799.1
	MTRF1L	NM_001114184.3		c.649A>G	p.Ser217Gly	missense	Exon 4 of 6	NP_001107656.1	Q9UGC7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTRF1L	ENST00000367233.10	TSL:1 MANE Select	c.649A>G	p.Ser217Gly	missense	Exon 4 of 7	ENSP00000356202.5	Q9UGC7-1
	MTRF1L	ENST00000367231.9	TSL:1	c.649A>G	p.Ser217Gly	missense	Exon 4 of 6	ENSP00000356200.5	Q9UGC7-2
	MTRF1L	ENST00000367230.5	TSL:1	c.541A>G	p.Ser181Gly	missense	Exon 4 of 6	ENSP00000356199.1	Q9UGC7-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459964 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726300

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4316

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111894

Other (OTH) AF: 0.00 AC: 0 AN: 60226

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.41
Sift	Benign	0.13	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.77		Loss of glycosylation at S217 (P = 0.0296)
MVP		0.47
MPC		1.3
ClinPred		0.80	D
GERP RS		5.2
PromoterAI		0.036	Neutral
Varity_R		0.65
gMVP		0.73
Mutation Taster		=52/48	polymorphism

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

hg19: chr6-153315686;