10-93692698-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145246.5(FRA10AC1):​c.328C>A​(p.Arg110Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000833 in 1,439,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

FRA10AC1
NM_145246.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.71

Publications

0 publications found
Variant links:
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 abnormalities
    Inheritance: 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 (BayesDel_noAF=-0.34).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRA10AC1NM_145246.5 linkc.328C>A p.Arg110Arg synonymous_variant Exon 6 of 14 ENST00000359204.5 NP_660289.2 Q70Z53-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRA10AC1ENST00000359204.5 linkc.328C>A p.Arg110Arg synonymous_variant Exon 6 of 14 1 NM_145246.5 ENSP00000360488.3 Q70Z53-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000833
AC:
12
AN:
1439890
Hom.:
0
Cov.:
28
AF XY:
0.0000112
AC XY:
8
AN XY:
716368
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31922
American (AMR)
AF:
0.00
AC:
0
AN:
40276
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25682
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37962
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82604
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53148
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
0.00000997
AC:
11
AN:
1103050
Other (OTH)
AF:
0.0000168
AC:
1
AN:
59516
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.421
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
CADD
Benign
13
DANN
Benign
0.69
PhyloP100
3.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs555127846; hg19: chr10-95452455; API