chr22-39513763-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_019008.6(MIEF1):c.832G>A(p.Ala278Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
MIEF1
NM_019008.6 missense
NM_019008.6 missense
Scores
4
7
7
Clinical Significance
Conservation
PhyloP100: 9.99
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 GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MIEF1 | NM_019008.6 | c.832G>A | p.Ala278Thr | missense_variant | 6/6 | ENST00000325301.7 | |
MIEF1 | NM_001304564.2 | c.832G>A | p.Ala278Thr | missense_variant | 6/7 | ||
MIEF1 | NR_130789.2 | n.1233G>A | non_coding_transcript_exon_variant | 6/6 | |||
MIEF1 | NR_130790.2 | n.1383G>A | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MIEF1 | ENST00000325301.7 | c.832G>A | p.Ala278Thr | missense_variant | 6/6 | 1 | NM_019008.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251212Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135852
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727234
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74330
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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 | May 05, 2023 | The c.832G>A (p.A278T) alteration is located in exon 6 (coding exon 4) of the MIEF1 gene. This alteration results from a G to A substitution at nucleotide position 832, causing the alanine (A) at amino acid position 278 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
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
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
D;D;D
Vest4
MutPred
Gain of glycosylation at A278 (P = 0.0306);Gain of glycosylation at A278 (P = 0.0306);Gain of glycosylation at A278 (P = 0.0306);
MVP
MPC
1.1
ClinPred
D
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