rs7999394

Variant names:

• chr13-41236495-G-A
• rs7999394
• NM_004294.4:c.871-2488C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004294.4(MTRF1):​c.871-2488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,038 control chromosomes in the GnomAD database, including 31,116 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31115 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: MTRF1 NM_004294.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

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.871-2488C>T		intron	N/A	NP_004285.2
	MTRF1	NM_001354073.1		c.871-2488C>T		intron	N/A	NP_001341002.1	O75570-1
	MTRF1	NM_001354074.1		c.871-2488C>T		intron	N/A	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.871-2488C>T		intron	N/A	ENSP00000368793.3	O75570-1
	MTRF1	ENST00000948294.1		c.997-2488C>T		intron	N/A	ENSP00000618353.1
	MTRF1	ENST00000948296.1		c.997-2488C>T		intron	N/A	ENSP00000618355.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96822 AN: 151918 Hom.: 31103 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.637 AC: 96870 AN: 152036 Hom.: 31115 Cov.: 32 AF XY: 0.640 AC XY: 47594 AN XY: 74340

African (AFR) AF: 0.612 AC: 25346 AN: 41440

American (AMR) AF: 0.658 AC: 10048 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2060 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2893 AN: 5184

South Asian (SAS) AF: 0.646 AC: 3118 AN: 4824

European-Finnish (FIN) AF: 0.709 AC: 7477 AN: 10544

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43942 AN: 67976

Other (OTH) AF: 0.616 AC: 1300 AN: 2112

Alfa AF: 0.640 Hom.: 15363

Bravo AF: 0.630

Asia WGS AF: 0.642 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs7999394; hg19: chr13-41810631;