dbSNP rs2236014: MTRF1L:c.*698T>C (chr6-152989197-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_019041.7(MTRF1L):c.*698T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0090 ( 2 hom., cov: 3)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MTRF1L
NM_019041.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

4 publications found

Variant links:

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]

MTRF1L links:

ENSG00000227627 (HGNC:):

ENSG00000227627 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTRF1L	NM_019041.7 link	c.*698T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000367233.10	NP_061914.3	Q9UGC7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTRF1L	ENST00000367233.10 link	c.*698T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_019041.7	ENSP00000356202.5		Q9UGC7-1

Frequencies

GnomAD3 genomes

AF:

0.00898

AC:

427

AN:

47554

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00871

Gnomad AMI

AF:

0.0170

Gnomad AMR

AF:

0.00962

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.0109

Gnomad SAS

AF:

0.0107

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0147

Gnomad NFE

AF:

0.00803

Gnomad OTH

AF:

0.00525

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00899

AC:

427

AN:

47522

Hom.:

Cov.:

AF XY:

0.00937

AC XY:

215

AN XY:

22938

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00872

AC:

AN:

3442

American (AMR)

AF:

0.00963

AC:

AN:

4776

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

1614

East Asian (EAS)

AF:

0.0109

AC:

AN:

2466

South Asian (SAS)

AF:

0.0106

AC:

AN:

1412

European-Finnish (FIN)

AF:

0.0132

AC:

AN:

3492

Middle Eastern (MID)

AF:

0.0164

AC:

AN:

122

European-Non Finnish (NFE)

AF:

0.00803

AC:

235

AN:

29258

Other (OTH)

AF:

0.00524

AC:

AN:

764

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.253

Heterozygous variant carriers

126

188

251

314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.157

Hom.:

240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.9

(source)

DANN

Benign

0.70

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over