rs776529563
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_016068.3(FIS1):c.430G>A(p.Gly144Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000313 in 1,596,516 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: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
FIS1
NM_016068.3 missense
NM_016068.3 missense
Scores
7
10
1
Clinical Significance
Conservation
PhyloP100: 6.05
Publications
1 publications found
Genes affected
FIS1 (HGNC:21689): (fission, mitochondrial 1) Enables identical protein binding activity. Involved in several processes, including calcium-mediated signaling using intracellular calcium source; cellular calcium ion homeostasis; and mitochondrion organization. Acts upstream of or within mitochondrion morphogenesis. Located in mitochondrion and peroxisome. Is integral component of mitochondrial outer membrane and integral component of peroxisomal membrane. Part of protein-containing complex. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.816
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_016068.3. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FIS1 | TSL:1 MANE Select | c.430G>A | p.Gly144Arg | missense | Exon 5 of 5 | ENSP00000223136.4 | Q9Y3D6 | ||
| FIS1 | TSL:1 | c.*86G>A | 3_prime_UTR | Exon 4 of 4 | ENSP00000442056.1 | F5H8A8 | |||
| FIS1 | TSL:1 | n.*156G>A | non_coding_transcript_exon | Exon 5 of 5 | ENSP00000444771.1 | F5H509 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152124
Hom.:
Cov.:
33
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:
GnomAD4 exome AF: 0.00000277 AC: 4AN: 1444392Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 716960 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1444392
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
716960
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33126
American (AMR)
AF:
AC:
0
AN:
42472
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25678
East Asian (EAS)
AF:
AC:
0
AN:
38818
South Asian (SAS)
AF:
AC:
0
AN:
83610
European-Finnish (FIN)
AF:
AC:
0
AN:
51830
Middle Eastern (MID)
AF:
AC:
0
AN:
5724
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1103450
Other (OTH)
AF:
AC:
0
AN:
59684
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74304 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152124
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74304
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41422
American (AMR)
AF:
AC:
0
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5174
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68020
Other (OTH)
AF:
AC:
0
AN:
2088
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of MoRF binding (P = 0.0011)
MVP
MPC
ClinPred
D
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
Publications
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