chr1-93550972-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001164473.3(FNBP1L):c.1677G>C(p.Met559Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00001 in 1,599,914 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
FNBP1L
NM_001164473.3 missense
NM_001164473.3 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 6.61
Genes affected
FNBP1L (HGNC:20851): (formin binding protein 1 like) The protein encoded by this gene binds to both CDC42 and N-WASP. This protein promotes CDC42-induced actin polymerization by activating the N-WASP-WIP complex and, therefore, is involved in a pathway that links cell surface signals to the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.34432834).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FNBP1L | NM_001164473.3 | c.1677G>C | p.Met559Ile | missense_variant | 16/17 | ENST00000271234.13 | |
FNBP1L | NM_001024948.3 | c.1503G>C | p.Met501Ile | missense_variant | 14/14 | ||
FNBP1L | NM_017737.5 | c.1503G>C | p.Met501Ile | missense_variant | 14/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FNBP1L | ENST00000271234.13 | c.1677G>C | p.Met559Ile | missense_variant | 16/17 | 5 | NM_001164473.3 | ||
FNBP1L | ENST00000260506.12 | c.1503G>C | p.Met501Ile | missense_variant | 14/14 | 1 | P4 | ||
FNBP1L | ENST00000370253.6 | c.1503G>C | p.Met501Ile | missense_variant | 14/15 | 5 | A1 | ||
FNBP1L | ENST00000424449.2 | c.1215G>C | p.Met405Ile | missense_variant | 11/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000124 AC: 3AN: 241666Hom.: 0 AF XY: 0.0000229 AC XY: 3AN XY: 131274
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GnomAD4 exome AF: 0.0000104 AC: 15AN: 1447704Hom.: 0 Cov.: 31 AF XY: 0.0000167 AC XY: 12AN XY: 719746
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74376
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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 | Sep 27, 2022 | The c.1677G>C (p.M559I) alteration is located in exon 16 (coding exon 16) of the FNBP1L gene. This alteration results from a G to C substitution at nucleotide position 1677, causing the methionine (M) at amino acid position 559 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.
REVEL
Benign
Sift
Benign
T;T;.;.
Sift4G
Benign
T;T;T;T
Polyphen
0.99, 0.29
.;D;.;B
Vest4
MutPred
Loss of ubiquitination at K560 (P = 0.0863);.;Loss of ubiquitination at K560 (P = 0.0863);.;
MVP
MPC
ClinPred
T
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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