chr5-108871481-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005246.4(FER):c.782A>G(p.Asn261Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,606,392 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 1 hom. )
Consequence
FER
NM_005246.4 missense
NM_005246.4 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 2.15
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.023656279).
BS2
?
High AC in GnomAd at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FER | NM_005246.4 | c.782A>G | p.Asn261Ser | missense_variant | 7/20 | ENST00000281092.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FER | ENST00000281092.9 | c.782A>G | p.Asn261Ser | missense_variant | 7/20 | 1 | NM_005246.4 | P1 | |
FER | ENST00000504143.6 | c.*253A>G | 3_prime_UTR_variant, NMD_transcript_variant | 5/18 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152142Hom.: 1 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000157 AC: 39AN: 249074Hom.: 1 AF XY: 0.000178 AC XY: 24AN XY: 134722
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GnomAD4 exome AF: 0.000100 AC: 146AN: 1454132Hom.: 1 Cov.: 29 AF XY: 0.0000982 AC XY: 71AN XY: 723334
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152260Hom.: 1 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74456
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ExAC
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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 | Mar 25, 2022 | The c.782A>G (p.N261S) alteration is located in exon 7 (coding exon 5) of the FER gene. This alteration results from a A to G substitution at nucleotide position 782, causing the asparagine (N) at amino acid position 261 to be replaced by a serine (S). 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
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N;N;N
PrimateAI
Benign
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