5-108832885-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005246.4(FER):āc.323A>Gā(p.Gln108Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,222 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 (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
FER
NM_005246.4 missense
NM_005246.4 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 8.47
Genes affected
FER (HGNC:3655): (FER tyrosine kinase) The protein encoded by this gene is a member of the FPS/FES family of non-transmembrane receptor tyrosine kinases. It regulates cell-cell adhesion and mediates signaling from the cell surface to the cytoskeleton via growth factor receptors. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome X. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41156596).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FER | NM_005246.4 | c.323A>G | p.Gln108Arg | missense_variant | 4/20 | ENST00000281092.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FER | ENST00000281092.9 | c.323A>G | p.Gln108Arg | missense_variant | 4/20 | 1 | NM_005246.4 | P1 | |
FER | ENST00000502752.1 | n.648A>G | non_coding_transcript_exon_variant | 5/8 | 1 | ||||
FER | ENST00000509035.5 | n.542A>G | non_coding_transcript_exon_variant | 3/3 | 3 | ||||
FER | ENST00000504143.6 | c.207+34496A>G | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247780Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134024
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GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455222Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 724028
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GnomAD4 genome Cov.: 31
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2022 | The c.323A>G (p.Q108R) alteration is located in exon 4 (coding exon 2) of the FER gene. This alteration results from a A to G substitution at nucleotide position 323, causing the glutamine (Q) at amino acid position 108 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
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;D
Polyphen
D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0606);Gain of MoRF binding (P = 0.0606);
MVP
MPC
ClinPred
D
GERP RS
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