chr10-93694874-A-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_145246.5(FRA10AC1):c.283T>G(p.Phe95Val) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,586,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F95L) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
FRA10AC1
NM_145246.5 missense
NM_145246.5 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 6.45
Publications
1 publications found
Genes affected
FRA10AC1 (HGNC:1162): (FRA10A associated CGG repeat 1) The protein encoded by this gene is a nuclear phosphoprotein of unknown function. This gene contains a tandem CGG repeat region within a CpG island that normally consists of 8-14 repeats but can expand to over 200 repeats. The repeat region is within the 5' UTR of some transcript variants, but is intronic to another variant. The expanded repeat allele is a fragile site and becomes hypermethylated, causing a reduction in gene expression. A disease phenotype has not been associated with expanded alleles. This gene is found within the rare FRA10A folate-sensitive fragile site. [provided by RefSeq, Dec 2016]
FRA10AC1 Gene-Disease associations (from GenCC):
- neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalitiesInheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
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=0.22915539).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000854 AC: 13AN: 152142Hom.: 0 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
13
AN:
152142
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: 0.000108 AC: 27AN: 250864 AF XY: 0.000118 show subpopulations
GnomAD2 exomes
AF:
AC:
27
AN:
250864
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: 0.000132 AC: 189AN: 1434564Hom.: 0 Cov.: 26 AF XY: 0.000130 AC XY: 93AN XY: 715460 show subpopulations
GnomAD4 exome
AF:
AC:
189
AN:
1434564
Hom.:
Cov.:
26
AF XY:
AC XY:
93
AN XY:
715460
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33204
American (AMR)
AF:
AC:
0
AN:
44556
Ashkenazi Jewish (ASJ)
AF:
AC:
54
AN:
25980
East Asian (EAS)
AF:
AC:
0
AN:
39534
South Asian (SAS)
AF:
AC:
0
AN:
85530
European-Finnish (FIN)
AF:
AC:
0
AN:
53384
Middle Eastern (MID)
AF:
AC:
1
AN:
5726
European-Non Finnish (NFE)
AF:
AC:
124
AN:
1087162
Other (OTH)
AF:
AC:
10
AN:
59488
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
9
18
28
37
46
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000854 AC: 13AN: 152142Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3AN XY: 74308 show subpopulations
GnomAD4 genome
AF:
AC:
13
AN:
152142
Hom.:
Cov.:
30
AF XY:
AC XY:
3
AN XY:
74308
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41442
American (AMR)
AF:
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
AC:
9
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
3
AN:
68024
Other (OTH)
AF:
AC:
1
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
7
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Jun 04, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.283T>G (p.F95V) alteration is located in exon 5 (coding exon 4) of the FRA10AC1 gene. This alteration results from a T to G substitution at nucleotide position 283, causing the phenylalanine (F) at amino acid position 95 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of ubiquitination at K96 (P = 0.1139);
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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