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GeneBe

22-39512408-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_019008.6(MIEF1):c.499G>A(p.Glu167Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MIEF1
NM_019008.6 missense

Scores

8
6
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MIEF1NM_019008.6 linkuse as main transcriptc.499G>A p.Glu167Lys missense_variant 5/6 ENST00000325301.7
MIEF1NM_001304564.2 linkuse as main transcriptc.499G>A p.Glu167Lys missense_variant 5/7
MIEF1NR_130789.2 linkuse as main transcriptn.900G>A non_coding_transcript_exon_variant 5/6
MIEF1NR_130790.2 linkuse as main transcriptn.1050G>A non_coding_transcript_exon_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MIEF1ENST00000325301.7 linkuse as main transcriptc.499G>A p.Glu167Lys missense_variant 5/61 NM_019008.6 P1Q9NQG6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461812
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 09, 2021The c.499G>A (p.E167K) alteration is located in exon 5 (coding exon 3) of the MIEF1 gene. This alteration results from a G to A substitution at nucleotide position 499, causing the glutamic acid (E) at amino acid position 167 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
Cadd
Pathogenic
30
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.097
T;T;T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.97
D;.;D
M_CAP
Benign
0.043
D
MetaRNN
Pathogenic
0.83
D;D;D
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.79
T
PROVEAN
Uncertain
-2.5
N;D;D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0080
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.86
MutPred
0.69
Gain of MoRF binding (P = 0.0021);Gain of MoRF binding (P = 0.0021);Gain of MoRF binding (P = 0.0021);
MVP
0.63
MPC
1.2
ClinPred
0.90
D
GERP RS
5.8
Varity_R
0.66
gMVP
0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-39908413; COSMIC: COSV57477740; COSMIC: COSV57477740; API