rs767520219

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001277313.2(FMN1):​c.4229G>T​(p.Arg1410Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1410H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FMN1
NM_001277313.2 missense

Scores

1
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.85
Variant links:
Genes affected
FMN1 (HGNC:3768): (formin 1) This gene belongs to the formin homology family and encodes a protein that has a role in the formation of adherens junction and the polymerization of linear actin cables. The homologous gene in mouse is associated with limb deformity. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33352268).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FMN1NM_001277313.2 linkc.4229G>T p.Arg1410Leu missense_variant Exon 21 of 21 ENST00000616417.5 NP_001264242.1 Q68DA7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FMN1ENST00000616417.5 linkc.4229G>T p.Arg1410Leu missense_variant Exon 21 of 21 5 NM_001277313.2 ENSP00000479134.1 Q68DA7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1447286
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
718504
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.05e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Uncertain
0.044
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T;.;T;T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.88
D
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.33
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.6
L;.;.;L
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-3.1
.;D;D;D
REVEL
Benign
0.14
Sift
Benign
0.10
.;T;D;D
Sift4G
Uncertain
0.055
T;D;D;T
Polyphen
0.96
.;D;.;.
Vest4
0.45
MutPred
0.31
.;Loss of MoRF binding (P = 0.0116);.;.;
MVP
0.74
MPC
0.19
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.49
gMVP
0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-33066542; API