chr1-93549303-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001164473.3(FNBP1L):c.1528G>A(p.Ala510Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000534 in 1,611,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )
Consequence
FNBP1L
NM_001164473.3 missense
NM_001164473.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.76
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 -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.090209424).
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FNBP1L | NM_001164473.3 | c.1528G>A | p.Ala510Thr | missense_variant | 15/17 | ENST00000271234.13 | |
FNBP1L | NM_001024948.3 | c.1354G>A | p.Ala452Thr | missense_variant | 13/14 | ||
FNBP1L | NM_017737.5 | c.1354G>A | p.Ala452Thr | missense_variant | 13/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FNBP1L | ENST00000271234.13 | c.1528G>A | p.Ala510Thr | missense_variant | 15/17 | 5 | NM_001164473.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152078Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247274Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134156
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GnomAD4 exome AF: 0.0000534 AC: 78AN: 1459500Hom.: 0 Cov.: 30 AF XY: 0.0000523 AC XY: 38AN XY: 726018
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74296
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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 | Jan 10, 2023 | The c.1528G>A (p.A510T) alteration is located in exon 15 (coding exon 15) of the FNBP1L gene. This alteration results from a G to A substitution at nucleotide position 1528, causing the alanine (A) at amino acid position 510 to be replaced by a threonine (T). 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
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T;D;T
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
0.11, 0.013
.;B;.;B
Vest4
MVP
MPC
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