chr22-39513877-G-C
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_019008.6(MIEF1):āc.946G>Cā(p.Val316Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000066 ( 0 hom., cov: 32)
Exomes š: 0.000021 ( 0 hom. )
Consequence
MIEF1
NM_019008.6 missense
NM_019008.6 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 4.14
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 Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.05188489).
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MIEF1 | NM_019008.6 | c.946G>C | p.Val316Leu | missense_variant | 6/6 | ENST00000325301.7 | |
MIEF1 | NM_001304564.2 | c.946G>C | p.Val316Leu | missense_variant | 6/7 | ||
MIEF1 | NR_130789.2 | n.1347G>C | non_coding_transcript_exon_variant | 6/6 | |||
MIEF1 | NR_130790.2 | n.1497G>C | non_coding_transcript_exon_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MIEF1 | ENST00000325301.7 | c.946G>C | p.Val316Leu | missense_variant | 6/6 | 1 | NM_019008.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251342Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135882
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461808Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727204
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74326
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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 | Dec 15, 2022 | The c.946G>C (p.V316L) alteration is located in exon 6 (coding exon 4) of the MIEF1 gene. This alteration results from a G to C substitution at nucleotide position 946, causing the valine (V) at amino acid position 316 to be replaced by a leucine (L). 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
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
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
B;B;B
Vest4
MutPred
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
MPC
0.34
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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