13-41217174-A-C

Position:

• chr13-41217174-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004294.4(MTRF1):​c.1279T>G​(p.Ser427Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00252 in 1,609,618 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (47 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (40 hom.)
• Consequence: MTRF1 NM_004294.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.24

Genes affected

MTRF1 (HGNC:7469): (mitochondrial translation release factor 1) The protein encoded by this gene was determined by in silico methods to be a mitochondrial protein with similarity to the peptide chain release factors (RFs) discovered in bacteria and yeast. The peptide chain release factors direct the termination of translation in response to the peptide chain termination codons. Initially thought to have a role in the termination of mitochondria protein synthesis, a recent publication found no mitochondrial translation release functionality. Multiple alternatively spliced transcript variants have been suggested by mRNA and EST data; however, their full-length natures are not clear. [provided by RefSeq, Jul 2008]

MTRF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035691261).
• BP6: Variant 13-41217174-A-C is Benign according to our data. Variant chr13-41217174-A-C is described in ClinVar as [Benign]. Clinvar id is 790675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2061/152288) while in subpopulation AFR AF= 0.0472 (1960/41538). AF 95% confidence interval is 0.0454. There are 47 homozygotes in gnomad4. There are 968 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTRF1	NM_004294.4	c.1279T>G	p.Ser427Ala	missense_variant	10/10	ENST00000379480.9	NP_004285.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTRF1	ENST00000379480.9	c.1279T>G	p.Ser427Ala	missense_variant	10/10	1	NM_004294.4	ENSP00000368793.3

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2062 AN: 152170 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00387 AC: 960 AN: 248306 Hom.: 31 AF XY: 0.00254 AC XY: 342 AN XY: 134498

Gnomad AFR exome AF: 0.0515

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000263

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00137 AC: 1992 AN: 1457330 Hom.: 40 Cov.: 29 AF XY: 0.00116 AC XY: 844 AN XY: 724880

Gnomad4 AFR exome AF: 0.0465

Gnomad4 AMR exome AF: 0.00274

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000820

Gnomad4 OTH exome AF: 0.00317

GnomAD4 genome AF: 0.0135 AC: 2061 AN: 152288 Hom.: 47 Cov.: 32 AF XY: 0.0130 AC XY: 968 AN XY: 74494

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00189 Hom.: 13

Bravo AF: 0.0154

ESP6500AA AF: 0.0477 AC: 210

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00468 AC: 568

Asia WGS AF: 0.00231 AC: 8 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Labcorp Genetics (formerly Invitae), Labcorp	Mar 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0025	T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.35	.;T
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.059
Sift	Benign	0.50	T;T
Sift4G	Benign	0.91	T;T
Polyphen		0.98	D;D
Vest4		0.22
MVP		0.32
MPC		0.10
ClinPred		0.038	T
GERP RS		5.5
Varity_R		0.091
gMVP		0.44

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

Other links and lift over

dbSNP: rs116450658; hg19: chr13-41791310;