rs782265090
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002024.6(FMR1):c.522T>A(p.Asn174Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,198,215 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 83 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000045 ( 0 hom., 4 hem., cov: 23)
Exomes 𝑓: 0.00011 ( 0 hom. 79 hem. )
Consequence
FMR1
NM_002024.6 missense
NM_002024.6 missense
Scores
1
3
9
Clinical Significance
Conservation
PhyloP100: 1.08
Genes affected
FMR1 (HGNC:3775): (fragile X messenger ribonucleoprotein 1) The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5' UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.016963959).
BP6
?
Variant X-147930136-T-A is Benign according to our data. Variant chrX-147930136-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 211029.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000448 (5/111610) while in subpopulation SAS AF= 0.00187 (5/2672). AF 95% confidence interval is 0.000737. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FMR1 | NM_002024.6 | c.522T>A | p.Asn174Lys | missense_variant | 7/17 | ENST00000370475.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FMR1 | ENST00000370475.9 | c.522T>A | p.Asn174Lys | missense_variant | 7/17 | 1 | NM_002024.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000448 AC: 5AN: 111610Hom.: 0 Cov.: 23 AF XY: 0.000118 AC XY: 4AN XY: 33804
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000235 AC: 43AN: 183260Hom.: 0 AF XY: 0.000487 AC XY: 33AN XY: 67768
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GnomAD4 exome AF: 0.000106 AC: 115AN: 1086605Hom.: 0 Cov.: 29 AF XY: 0.000224 AC XY: 79AN XY: 352711
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GnomAD4 genome ? AF: 0.0000448 AC: 5AN: 111610Hom.: 0 Cov.: 23 AF XY: 0.000118 AC XY: 4AN XY: 33804
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 06, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;T;T;.;T;T;T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;.;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.53, 0.088, 0.13, 0.040
.;.;.;P;.;B;B;B;B;.;.;.
Vest4
MutPred
Gain of ubiquitination at N174 (P = 0.0219);Gain of ubiquitination at N174 (P = 0.0219);Gain of ubiquitination at N174 (P = 0.0219);Gain of ubiquitination at N174 (P = 0.0219);Gain of ubiquitination at N174 (P = 0.0219);Gain of ubiquitination at N174 (P = 0.0219);Gain of ubiquitination at N174 (P = 0.0219);Gain of ubiquitination at N174 (P = 0.0219);Gain of ubiquitination at N174 (P = 0.0219);Gain of ubiquitination at N174 (P = 0.0219);.;Gain of ubiquitination at N174 (P = 0.0219);
MVP
MPC
1.1
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at