chr5-108867811-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_005246.4(FER):c.526A>G(p.Met176Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
FER
NM_005246.4 missense
NM_005246.4 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 6.69
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.27393484).
BS2
?
High AC in GnomAdExome at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FER | NM_005246.4 | c.526A>G | p.Met176Val | missense_variant | 6/20 | ENST00000281092.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FER | ENST00000281092.9 | c.526A>G | p.Met176Val | missense_variant | 6/20 | 1 | NM_005246.4 | P1 | |
FER | ENST00000504143.6 | c.252A>G | p.Gln84= | synonymous_variant, NMD_transcript_variant | 4/18 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151940Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250692Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135490
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461146Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 726850
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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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 | Feb 05, 2024 | The c.526A>G (p.M176V) alteration is located in exon 6 (coding exon 4) of the FER gene. This alteration results from a A to G substitution at nucleotide position 526, causing the methionine (M) at amino acid position 176 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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