rs7999394

Positions:

• chr13-41236495-G-A

Variant summary

Our verdict is Benign. Variant got -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

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)

LOC101929140 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTRF1	NM_004294.4	c.871-2488C>T		intron_variant		ENST00000379480.9	NP_004285.2
LOC101929140	NR_120423.1	n.1730G>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTRF1	ENST00000379480.9	c.871-2488C>T		intron_variant		1	NM_004294.4	ENSP00000368793	P1
KBTBD6-DT	ENST00000619407.4	n.1719G>A		non_coding_transcript_exon_variant	4/4	2
MTRF1	ENST00000379477.5	c.871-2488C>T		intron_variant		2		ENSP00000368790	P1
KBTBD6-DT	ENST00000661006.1	n.1625G>A		non_coding_transcript_exon_variant	3/3

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

Gnomad4 NFE exome AF: 1.00

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

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.616

Alfa AF: 0.642 Hom.: 13699

Bravo AF: 0.630

Asia WGS AF: 0.642 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.64

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: rs7999394; hg19: chr13-41810631;