9-129902949-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015033.3(FNBP1):​c.1348G>A​(p.Asp450Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FNBP1
NM_015033.3 missense

Scores

6
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
FNBP1 (HGNC:17069): (formin binding protein 1) The protein encoded by this gene is a member of the formin-binding-protein family. The protein contains an N-terminal Fer/Cdc42-interacting protein 4 (CIP4) homology (FCH) domain followed by a coiled-coil domain, a proline-rich motif, a second coiled-coil domain, a Rho family protein-binding domain (RBD), and a C-terminal SH3 domain. This protein binds sorting nexin 2 (SNX2), tankyrase (TNKS), and dynamin; an interaction between this protein and formin has not been demonstrated yet in human. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FNBP1NM_015033.3 linkc.1348G>A p.Asp450Asn missense_variant Exon 13 of 17 ENST00000446176.7 NP_055848.1 Q96RU3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FNBP1ENST00000446176.7 linkc.1348G>A p.Asp450Asn missense_variant Exon 13 of 17 1 NM_015033.3 ENSP00000413625.1 Q96RU3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000421
AC:
1
AN:
237770
Hom.:
0
AF XY:
0.00000776
AC XY:
1
AN XY:
128932
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000936
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 06, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1348G>A (p.D450N) alteration is located in exon 13 (coding exon 13) of the FNBP1 gene. This alteration results from a G to A substitution at nucleotide position 1348, causing the aspartic acid (D) at amino acid position 450 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.51
D;.;.;.
Eigen
Uncertain
0.61
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.97
D;D;D;D
M_CAP
Benign
0.035
D
MetaRNN
Pathogenic
0.80
D;D;D;D
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.2
M;.;.;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-4.6
D;.;.;D
REVEL
Benign
0.26
Sift
Benign
0.19
T;.;.;T
Sift4G
Pathogenic
0.0
D;T;D;T
Polyphen
0.93
P;D;.;P
Vest4
0.72
MutPred
0.51
Loss of helix (P = 0.1299);.;.;.;
MVP
0.80
MPC
0.59
ClinPred
0.99
D
GERP RS
5.8
Varity_R
0.46
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs776554206; hg19: chr9-132665228; API