5-179550595-C-A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_025158.5(RUFY1):c.26C>A(p.Ala9Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,223,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9V) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.0000083 ( 0 hom., cov: 35)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RUFY1
NM_025158.5 missense
NM_025158.5 missense
Scores
1
17
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.784
Publications
0 publications found
Genes affected
RUFY1 (HGNC:19760): (RUN and FYVE domain containing 1) This gene encodes a protein that contains a RUN domain and a FYVE-type zinc finger domain. The encoded protein binds to phosphatidylinositol-3-phosphate (PI3P) and plays a role in early endosomal trafficking, tethering and fusion through interactions with small GTPases including Rab4, Rab5 and Rab14. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07134399).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RUFY1 | ENST00000319449.9 | c.26C>A | p.Ala9Asp | missense_variant | Exon 1 of 18 | 1 | NM_025158.5 | ENSP00000325594.4 | ||
| RUFY1 | ENST00000393448.6 | n.-242C>A | upstream_gene_variant | 1 | ENSP00000377094.2 | |||||
| RUFY1 | ENST00000502984.5 | c.-245C>A | upstream_gene_variant | 3 | ENSP00000425533.1 |
Frequencies
GnomAD3 genomes 0.00000830 AC: 1AN: 120550Hom.: 0 Cov.: 35 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
120550
Hom.:
Cov.:
35
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: 0.00000163 AC: 2AN: 1223818Hom.: 0 Cov.: 35 AF XY: 0.00000333 AC XY: 2AN XY: 601226 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1223818
Hom.:
Cov.:
35
AF XY:
AC XY:
2
AN XY:
601226
show subpopulations
African (AFR)
AF:
AC:
0
AN:
24646
American (AMR)
AF:
AC:
0
AN:
21256
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19650
East Asian (EAS)
AF:
AC:
0
AN:
26242
South Asian (SAS)
AF:
AC:
0
AN:
58690
European-Finnish (FIN)
AF:
AC:
0
AN:
28580
Middle Eastern (MID)
AF:
AC:
0
AN:
3644
European-Non Finnish (NFE)
AF:
AC:
2
AN:
992278
Other (OTH)
AF:
AC:
0
AN:
48832
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000830 AC: 1AN: 120550Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 58918 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
120550
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
58918
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:
27686
American (AMR)
AF:
AC:
0
AN:
12892
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2968
East Asian (EAS)
AF:
AC:
0
AN:
4614
South Asian (SAS)
AF:
AC:
0
AN:
3926
European-Finnish (FIN)
AF:
AC:
0
AN:
8230
Middle Eastern (MID)
AF:
AC:
0
AN:
250
European-Non Finnish (NFE)
AF:
AC:
1
AN:
57436
Other (OTH)
AF:
AC:
0
AN:
1698
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), 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
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0215);
MVP
MPC
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
Publications
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