rs146321570

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005892.4(FMNL1):​c.1226C>A​(p.Ala409Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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. A409V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FMNL1
NM_005892.4 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30
Variant links:
Genes affected
FMNL1 (HGNC:1212): (formin like 1) This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. An alternative splice variant has been described but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]
FMNL1-AS1 (HGNC:55717): (FMNL1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1561186).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FMNL1NM_005892.4 linkc.1226C>A p.Ala409Glu missense_variant Exon 12 of 27 ENST00000331495.8 NP_005883.3 O95466-1
FMNL1NM_001411128.1 linkc.1226C>A p.Ala409Glu missense_variant Exon 12 of 26 NP_001398057.1
FMNL1-AS1NR_186807.1 linkn.825+325G>T intron_variant Intron 1 of 1
FMNL1-AS1NR_186808.1 linkn.661-17G>T intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FMNL1ENST00000331495.8 linkc.1226C>A p.Ala409Glu missense_variant Exon 12 of 27 1 NM_005892.4 ENSP00000329219.2 O95466-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249588
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134908
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:
0.00000888
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460608
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726568
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.029
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.23
T;T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.53
FATHMM_MKL
Benign
0.37
N
LIST_S2
Benign
0.85
T;T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.72
T
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.9
N;.
REVEL
Benign
0.22
Sift
Uncertain
0.011
D;.
Sift4G
Benign
0.54
T;T
Polyphen
0.22
B;.
Vest4
0.25
MutPred
0.47
Gain of disorder (P = 0.0546);.;
MVP
0.44
MPC
0.68
ClinPred
0.63
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.31
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs146321570; hg19: chr17-43317988; API