chr22-39512486-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_019008.6(MIEF1):c.577G>A(p.Asp193Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,458,198 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000017 ( 1 hom. )
Consequence
MIEF1
NM_019008.6 missense
NM_019008.6 missense
Scores
3
4
11
Clinical Significance
Conservation
PhyloP100: 9.59
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MIEF1 | NM_019008.6 | c.577G>A | p.Asp193Asn | missense_variant | 5/6 | ENST00000325301.7 | |
MIEF1 | NM_001304564.2 | c.577G>A | p.Asp193Asn | missense_variant | 5/7 | ||
MIEF1 | NR_130789.2 | n.978G>A | non_coding_transcript_exon_variant | 5/6 | |||
MIEF1 | NR_130790.2 | n.1128G>A | non_coding_transcript_exon_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MIEF1 | ENST00000325301.7 | c.577G>A | p.Asp193Asn | missense_variant | 5/6 | 1 | NM_019008.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000483 AC: 12AN: 248592Hom.: 1 AF XY: 0.0000520 AC XY: 7AN XY: 134590
GnomAD3 exomes
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12
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248592
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AN XY:
134590
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1458198Hom.: 1 Cov.: 32 AF XY: 0.0000207 AC XY: 15AN XY: 724950
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
AF:
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4
Asia WGS
AF:
AC:
3
AN:
3478
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 submitter | clinical testing | Ambry Genetics | Oct 25, 2023 | The c.577G>A (p.D193N) 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 577, causing the aspartic acid (D) at amino acid position 193 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
D;P;P
Vest4
MutPred
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
MPC
0.69
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at