dbSNP rs769059682: MIEF1:p.Arg144Gly (chr22-39512339-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_019008.6(MIEF1):c.430C>G(p.Arg144Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R144P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MIEF1
NM_019008.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.82

Publications

0 publications found

Variant links:

Genes affected

MIEF1 (HGNC:25979): (mitochondrial elongation factor 1) Enables ADP binding activity; GDP binding activity; and identical protein binding activity. Involved in several processes, including positive regulation of mitochondrial fission; positive regulation of mitochondrial translation; and positive regulation of protein targeting to membrane. Located in mitochondrial matrix and mitochondrial outer membrane. Colocalizes with mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

MIEF1 Gene-Disease associations (from GenCC):

optic atrophy 14
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

MIEF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36924988).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019008.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIEF1	NM_019008.6	MANE Select	c.430C>G	p.Arg144Gly	missense	Exon 5 of 6	NP_061881.2
MIEF1	NM_001304564.2		c.430C>G	p.Arg144Gly	missense	Exon 5 of 7	NP_001291493.1	B0QY95
MIEF1	NR_130789.2		n.831C>G		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIEF1	ENST00000325301.7	TSL:1 MANE Select	c.430C>G	p.Arg144Gly	missense	Exon 5 of 6	ENSP00000327124.2	Q9NQG6-1
MIEF1	ENST00000402881.5	TSL:1	c.430C>G	p.Arg144Gly	missense	Exon 5 of 7	ENSP00000385110.1	B0QY95
MIEF1	ENST00000433117.6	TSL:1	n.344C>G		non_coding_transcript_exon	Exon 5 of 6	ENSP00000404096.2	Q9NQG6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Benign

0.0089

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

3.8

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.098

Sift

Uncertain

0.029

Sift4G

Uncertain

0.046

Polyphen

0.72

Vest4

0.68

MutPred

0.29

Loss of MoRF binding (P = 0.0436)

MVP

0.32

MPC

0.61

ClinPred

0.83

GERP RS

5.8

Varity_R

0.69

gMVP

0.26

Mutation Taster

=23/77

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over