5-179550633-C-T
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.64C>T(p.Pro22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000718 in 1,393,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000099 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000070 ( 0 hom. )
Consequence
RUFY1
NM_025158.5 missense
NM_025158.5 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.139
Publications
1 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=0.077283084).
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RUFY1 | ENST00000319449.9 | c.64C>T | p.Pro22Ser | missense_variant | Exon 1 of 18 | 1 | NM_025158.5 | ENSP00000325594.4 | ||
| RUFY1 | ENST00000393448.6 | n.-204C>T | upstream_gene_variant | 1 | ENSP00000377094.2 | |||||
| RUFY1 | ENST00000502984.5 | c.-207C>T | upstream_gene_variant | 3 | ENSP00000425533.1 |
Frequencies
GnomAD3 genomes 0.00000987 AC: 1AN: 101278Hom.: 0 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
101278
Hom.:
Cov.:
30
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:
GnomAD2 exomes AF: 0.0000107 AC: 1AN: 93374 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
93374
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000696 AC: 9AN: 1292228Hom.: 0 Cov.: 35 AF XY: 0.00000470 AC XY: 3AN XY: 638248 show subpopulations
GnomAD4 exome
AF:
AC:
9
AN:
1292228
Hom.:
Cov.:
35
AF XY:
AC XY:
3
AN XY:
638248
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26100
American (AMR)
AF:
AC:
1
AN:
27440
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
21950
East Asian (EAS)
AF:
AC:
0
AN:
26628
South Asian (SAS)
AF:
AC:
0
AN:
70330
European-Finnish (FIN)
AF:
AC:
0
AN:
31786
Middle Eastern (MID)
AF:
AC:
1
AN:
4512
European-Non Finnish (NFE)
AF:
AC:
7
AN:
1031178
Other (OTH)
AF:
AC:
0
AN:
52304
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.447
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000987 AC: 1AN: 101278Hom.: 0 Cov.: 30 AF XY: 0.0000204 AC XY: 1AN XY: 48968 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
101278
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
48968
show subpopulations
African (AFR)
AF:
AC:
0
AN:
25340
American (AMR)
AF:
AC:
0
AN:
8526
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2640
East Asian (EAS)
AF:
AC:
0
AN:
2122
South Asian (SAS)
AF:
AC:
0
AN:
2806
European-Finnish (FIN)
AF:
AC:
0
AN:
6966
Middle Eastern (MID)
AF:
AC:
0
AN:
216
European-Non Finnish (NFE)
AF:
AC:
1
AN:
50594
Other (OTH)
AF:
AC:
0
AN:
1372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
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:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Oct 04, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.64C>T (p.P22S) alteration is located in exon 1 (coding exon 1) of the RUFY1 gene. This alteration results from a C to T substitution at nucleotide position 64, causing the proline (P) at amino acid position 22 to be replaced by a serine (S). 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
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
L
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of phosphorylation at P22 (P = 0.0033);
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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