rs772552456
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_145246.5(FRA10AC1):c.379T>C(p.Trp127Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,581,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
FRA10AC1
NM_145246.5 missense, splice_region
NM_145246.5 missense, splice_region
Scores
11
6
2
Splicing: ADA: 0.9337
1
1
Clinical Significance
Conservation
PhyloP100: 8.81
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: Likely_pathogenic. The variant received 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.988
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152138Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152138
Hom.:
Cov.:
31
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: 0.0000119 AC: 17AN: 1429276Hom.: 0 Cov.: 25 AF XY: 0.00000842 AC XY: 6AN XY: 712336 show subpopulations
GnomAD4 exome
AF:
AC:
17
AN:
1429276
Hom.:
Cov.:
25
AF XY:
AC XY:
6
AN XY:
712336
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32000
American (AMR)
AF:
AC:
0
AN:
41150
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25724
East Asian (EAS)
AF:
AC:
0
AN:
38696
South Asian (SAS)
AF:
AC:
0
AN:
83414
European-Finnish (FIN)
AF:
AC:
0
AN:
53256
Middle Eastern (MID)
AF:
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
AC:
14
AN:
1090190
Other (OTH)
AF:
AC:
3
AN:
59150
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
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 0.0000131 AC: 2AN: 152138Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74312 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152138
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74312
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41438
American (AMR)
AF:
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5196
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68000
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
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
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Apr 04, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.379T>C (p.W127R) alteration is located in exon 6 (coding exon 5) of the FRA10AC1 gene. This alteration results from a T to C substitution at nucleotide position 379, causing the tryptophan (W) at amino acid position 127 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0037);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
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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