10-93692719-T-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS1_Supporting
The NM_145246.5(FRA10AC1):c.307A>G(p.Lys103Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,579,700 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00021 ( 1 hom. )
Consequence
FRA10AC1
NM_145246.5 missense
NM_145246.5 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 7.56
Publications
0 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_benign. The variant received -1 ACMG points.
BS1
Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00021 (300/1427396) while in subpopulation SAS AF = 0.000975 (78/80010). AF 95% confidence interval is 0.0008. There are 1 homozygotes in GnomAdExome4. There are 171 alleles in the male GnomAdExome4 subpopulation. Median coverage is 27. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000723 AC: 11AN: 152186Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
11
AN:
152186
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:
GnomAD2 exomes AF: 0.000168 AC: 37AN: 220058 AF XY: 0.000192 show subpopulations
GnomAD2 exomes
AF:
AC:
37
AN:
220058
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: 0.000210 AC: 300AN: 1427396Hom.: 1 Cov.: 27 AF XY: 0.000241 AC XY: 171AN XY: 709962 show subpopulations
GnomAD4 exome
AF:
AC:
300
AN:
1427396
Hom.:
Cov.:
27
AF XY:
AC XY:
171
AN XY:
709962
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31180
American (AMR)
AF:
AC:
1
AN:
37010
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25254
East Asian (EAS)
AF:
AC:
0
AN:
37742
South Asian (SAS)
AF:
AC:
78
AN:
80010
European-Finnish (FIN)
AF:
AC:
0
AN:
52972
Middle Eastern (MID)
AF:
AC:
0
AN:
5688
European-Non Finnish (NFE)
AF:
AC:
217
AN:
1098442
Other (OTH)
AF:
AC:
4
AN:
59098
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.451
Heterozygous variant carriers
0
13
26
39
52
65
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000722 AC: 11AN: 152304Hom.: 0 Cov.: 31 AF XY: 0.0000806 AC XY: 6AN XY: 74476 show subpopulations
GnomAD4 genome
AF:
AC:
11
AN:
152304
Hom.:
Cov.:
31
AF XY:
AC XY:
6
AN XY:
74476
show subpopulations
African (AFR)
AF:
AC:
4
AN:
41576
American (AMR)
AF:
AC:
0
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5176
South Asian (SAS)
AF:
AC:
3
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
4
AN:
68012
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.534
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
2
ExAC
AF:
AC:
24
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Sep 22, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.307A>G (p.K103E) alteration is located in exon 6 (coding exon 5) of the FRA10AC1 gene. This alteration results from a A to G substitution at nucleotide position 307, causing the lysine (K) at amino acid position 103 to be replaced by a glutamic acid (E). 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
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
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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