rs1324997610
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_025158.5(RUFY1):c.13G>A(p.Glu5Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,101,658 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000073 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000010 ( 1 hom. )
Consequence
RUFY1
NM_025158.5 missense
NM_025158.5 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.29
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=0.14639273).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000364 AC: 1AN: 27454Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
27454
Hom.:
Cov.:
0
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: 0.00 AC: 0AN: 45722 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
45722
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: 0.0000102 AC: 11AN: 1074196Hom.: 1 Cov.: 35 AF XY: 0.00000762 AC XY: 4AN XY: 525120 show subpopulations
GnomAD4 exome
AF:
AC:
11
AN:
1074196
Hom.:
Cov.:
35
AF XY:
AC XY:
4
AN XY:
525120
show subpopulations
African (AFR)
AF:
AC:
0
AN:
21152
American (AMR)
AF:
AC:
0
AN:
15310
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
16314
East Asian (EAS)
AF:
AC:
2
AN:
22740
South Asian (SAS)
AF:
AC:
0
AN:
45912
European-Finnish (FIN)
AF:
AC:
0
AN:
23844
Middle Eastern (MID)
AF:
AC:
0
AN:
3002
European-Non Finnish (NFE)
AF:
AC:
9
AN:
883770
Other (OTH)
AF:
AC:
0
AN:
42152
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000728 AC: 2AN: 27462Hom.: 0 Cov.: 0 AF XY: 0.0000756 AC XY: 1AN XY: 13226 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
2
AN:
27462
Hom.:
Cov.:
0
AF XY:
AC XY:
1
AN XY:
13226
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
3876
American (AMR)
AF:
AC:
1
AN:
1830
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
660
East Asian (EAS)
AF:
AC:
0
AN:
208
South Asian (SAS)
AF:
AC:
0
AN:
658
European-Finnish (FIN)
AF:
AC:
0
AN:
2540
Middle Eastern (MID)
AF:
AC:
0
AN:
50
European-Non Finnish (NFE)
AF:
AC:
0
AN:
17022
Other (OTH)
AF:
AC:
0
AN:
358
⚠️ 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: 0.325
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.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Mar 20, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.13G>A (p.E5K) alteration is located in exon 1 (coding exon 1) of the RUFY1 gene. This alteration results from a G to A substitution at nucleotide position 13, causing the glutamic acid (E) at amino acid position 5 to be replaced by a lysine (K). 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
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
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 MoRF binding (P = 5e-04);
MVP
MPC
ClinPred
D
GERP RS
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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