NM_004294.4:c.1279T>G

Variant names:

• chr13-41217174-A-C
• rs116450658
• NM_004294.4:c.1279T>G

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict 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
• Publications: 2 publications found

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]

KBTBD6-DT (HGNC:56824): (KBTBD6 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004294.4. 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
	MTRF1	NM_004294.4	MANE Select	c.1279T>G	p.Ser427Ala	missense	Exon 10 of 10	NP_004285.2
	MTRF1	NM_001354073.1		c.1279T>G	p.Ser427Ala	missense	Exon 15 of 15	NP_001341002.1	O75570-1
	MTRF1	NM_001354074.1		c.1279T>G	p.Ser427Ala	missense	Exon 10 of 10	NP_001341003.1	O75570-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTRF1	ENST00000379480.9	TSL:1 MANE Select	c.1279T>G	p.Ser427Ala	missense	Exon 10 of 10	ENSP00000368793.3	O75570-1
	MTRF1	ENST00000948294.1		c.1405T>G	p.Ser469Ala	missense	Exon 12 of 12	ENSP00000618353.1
	MTRF1	ENST00000948296.1		c.1405T>G	p.Ser469Ala	missense	Exon 12 of 12	ENSP00000618355.1

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

GnomAD2 exomes AF: 0.00387 AC: 960 AN: 248306 AF XY: 0.00254

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 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

African (AFR) AF: 0.0465 AC: 1556 AN: 33432

American (AMR) AF: 0.00274 AC: 122 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39480

South Asian (SAS) AF: 0.000152 AC: 13 AN: 85286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53196

Middle Eastern (MID) AF: 0.00331 AC: 19 AN: 5744

European-Non Finnish (NFE) AF: 0.0000820 AC: 91 AN: 1109416

Other (OTH) AF: 0.00317 AC: 191 AN: 60162

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

African (AFR) AF: 0.0472 AC: 1960 AN: 41538

American (AMR) AF: 0.00510 AC: 78 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00250 Hom.: 15

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.2
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.059
Sift	Benign	0.50	T
Sift4G	Benign	0.91	T
Polyphen		0.98	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
Mutation Taster		=99/1	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

dbSNP: rs116450658; hg19: chr13-41791310;