rs756361109
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_004208.4(AIFM1):āc.134C>Gā(p.Pro45Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000298 in 1,209,501 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.000063 ( 0 hom., 1 hem., cov: 22)
Exomes š: 0.000026 ( 0 hom. 11 hem. )
Consequence
AIFM1
NM_004208.4 missense
NM_004208.4 missense
Scores
7
5
Clinical Significance
Conservation
PhyloP100: 6.04
Genes affected
AIFM1 (HGNC:8768): (apoptosis inducing factor mitochondria associated 1) This gene encodes a flavoprotein essential for nuclear disassembly in apoptotic cells, and it is found in the mitochondrial intermembrane space in healthy cells. Induction of apoptosis results in the translocation of this protein to the nucleus where it affects chromosome condensation and fragmentation. In addition, this gene product induces mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Mutations in this gene cause combined oxidative phosphorylation deficiency 6 (COXPD6), a severe mitochondrial encephalomyopathy, as well as Cowchock syndrome, also known as X-linked recessive Charcot-Marie-Tooth disease-4 (CMTX-4), a disorder resulting in neuropathy, and axonal and motor-sensory defects with deafness and cognitive disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 10. [provided by RefSeq, Aug 2015]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
?
Variant X-130156576-G-C is Benign according to our data. Variant chrX-130156576-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 214085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Hemizygotes in GnomAdExome4 at 11 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIFM1 | NM_004208.4 | c.134C>G | p.Pro45Arg | missense_variant | 2/16 | ENST00000287295.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIFM1 | ENST00000287295.8 | c.134C>G | p.Pro45Arg | missense_variant | 2/16 | 1 | NM_004208.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000628 AC: 7AN: 111445Hom.: 0 Cov.: 22 AF XY: 0.0000297 AC XY: 1AN XY: 33695
GnomAD3 genomes
?
AF:
AC:
7
AN:
111445
Hom.:
Cov.:
22
AF XY:
AC XY:
1
AN XY:
33695
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000327 AC: 6AN: 183476Hom.: 0 AF XY: 0.0000736 AC XY: 5AN XY: 67910
GnomAD3 exomes
AF:
AC:
6
AN:
183476
Hom.:
AF XY:
AC XY:
5
AN XY:
67910
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000264 AC: 29AN: 1098056Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 11AN XY: 363420
GnomAD4 exome
AF:
AC:
29
AN:
1098056
Hom.:
Cov.:
30
AF XY:
AC XY:
11
AN XY:
363420
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000628 AC: 7AN: 111445Hom.: 0 Cov.: 22 AF XY: 0.0000297 AC XY: 1AN XY: 33695
GnomAD4 genome
?
AF:
AC:
7
AN:
111445
Hom.:
Cov.:
22
AF XY:
AC XY:
1
AN XY:
33695
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
5
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | AIFM1: BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 07, 2018 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Combined oxidative phosphorylation deficiency;CN118851:Charcot-Marie-Tooth Neuropathy X Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T
Polyphen
1.0
.;D
Vest4
MVP
MPC
1.2
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at